Composition for treatment of undifferentiated gastric cancer

ABSTRACT

Disclosed are: a therapeutic agent, a kit and a treatment method for undifferentiated gastric cancer; and a pharmaceutical composition, a kit and a treatment method which are more effective on a living organism having at least one cell selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing a mutant FGFR2. A combination of a FGFR2 inhibitor and a therapeutic substance for gastric cancer is more effective on undifferentiated gastric cancer. The combination of a FGFR2 inhibitor and a therapeutic substance for gastric cancer is more effective on a living organism having at least one cell selected from the group consisting of a cell overexpressing FGFR2 and a cell expressing a mutant FGFR2.

FIELD OF THE INVENTION

The present invention relates to a therapeutic agent, a kit and atherapeutic method for undifferentiated gastric cancer. The therapeuticagent comprises a combination of a substance having the activity ofinhibiting the kinase activity of a fibroblast growth factor receptor 2(hereinafter also referred to as “FGFR2”) and a therapeutic substancefor gastric cancer or a FGFR2 inhibitor different from the former FGFR2inhibitor. The substance having such inhibitory activity is hereinafteralso referred to as a “FGFR2 inhibitor”. The present invention relatesto use of a FGFR2 inhibitor for producing the therapeutic agent and to aFGFR2 inhibitor for the therapeutic agent.

In addition, the present invention relates to a pharmaceuticalcomposition and a kit comprising a combination of a FGFR2 inhibitor foradministration to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2 and a therapeutic substance for gastric canceror a FGFR2 inhibitor different from the former FGFR2 inhibitor, to atherapeutic method for a disease characterized by administeringeffective dosages of a FGFR2 inhibitor and a therapeutic substance forgastric cancer or a FGFR2 inhibitor different from the former FGFR2inhibitor to the living organism, to use of a FGFR2 inhibitor forproducing the pharmaceutical composition and to a FGFR2 inhibitor forthe pharmaceutical composition.

BACKGROUND OF THE INVENTION

Gastric cancer is one of the major cancers that cause death. Gastriccancers are histopathologically classified into differentiated gastriccancers and undifferentiated gastric cancers, where the latter includespoorly differentiated adenocarcinoma, signet-ring cell carcinoma,mucinous carcinoma and the like.

In the case of undifferentiated gastric cancer, cancer cells are likelyto diffuse and also likely to develop fibrosis that leads to scirrhousgastric cancer. Undifferentiated gastric cancer is commonly observed inyoung people, and is known to cause invasive proliferation andmetastasis, indicating a poor prognosis⁽¹⁾.

FGFR2 (also referred to as “K-sam”) is amplified in diffuse-type gastriccancer, namely, undifferentiated gastric cancer and is known to beinvolved in malignant alteration of cancer^((1,2)). FGFR2 gene isreported to be amplified in 33% of patients with undifferentiatedgastric cancer⁽²⁾, and FGFR2 is reported to be positive in about 50% ofpatients with undifferentiated gastric cancer⁽¹⁾. FGFR2 gene inducestransformation of NIH3T3 cell, and the transformed cell is reported toshow tumorigenicity in nude mice⁽³⁾. Furthermore, FGFR2 truncated atC-terminal is reported to have a strong transformation activity andpredominantly expressed in undifferentiated gastric cancer cellline^((1,3))). For example, FGFR2 having residues downstream fromtyrosine at 769 deleted is reported to have a high transformationactivity⁽³⁾.

It is also reported that FGFR2 gene is amplified in poorlydifferentiated gastric cancer, particularly scirrhous gastric cancer,while FGFR2 protein having C-terminal (including tyrosine residues 780,784 and 813) deleted is specifically expressed in scirrhous gastriccancer⁽⁴⁾. Amplification of activated FGFR2 is reported to cause tumorgrowth in scirrhous gastric cancer⁽⁴⁾.

Examples of conventionally-used chemotherapeutic substances for gastriccancer include 5-fluorouracil analogs and paclitaxel analogs. None ofthem, however, have satisfactory anti-tumor effect and thus there hasbeen a strong need for development of a novel anti-tumor agent.

A FGFR2 inhibitor, diphenylamine derivative, is recently reported todose-dependently suppress cell growth of a human scirrhous gastric cellline and show anti-tumor effect on a subcutaneous transplanted(xenograft) model of human scirrhous gastric cell line⁽⁵⁾.

A FGFR2 inhibitor,4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,is suggested to be effective on gastric cancer overexpressing K-sam⁽⁶⁾.

Accordingly, a FGFR2 inhibitor is suggested to show antiproliferativeaction and anti-tumor effect on undifferentiated gastric cancers,preferably poorly differentiated adenocarcinoma, signet-ring cellcarcinoma, mucinous carcinoma and scirrhous gastric cancer.

Here, a compound represented by General Formula (I) is known as anantiangiogenic substance⁽⁷⁻⁹⁾. However, there is no report that thecompound represented by General Formula (I) has a FGFR2 inhibitoryactivity.

Moreover, there has been no report as to whether a combination of thesecompounds will bring any effect.

REFERENCES

(1) Clinical Cancer Research. 2(8), 1373-1381, 1996.

(2) Journal of Cancer Research and Clinical Oncology. 127, 207-216,2001.

(3) Cancer Research. 54, 3237-3241, 1994.

(4) Cancer Research. 59(24), 6080-6086, 1999.

(5) Bioorganic and Medicinal Chemistry Letters. 14(4), 875-879, 2004.

(6) Proceeding of the American Association for Cancer Research. 47, 890,2006.

(7) International Publication No. WO02/32872

(8) International Publication No. WO2004/080462

(9) International Publication No. WO2005/063713

DISCLOSURE OF THE INVENTION

The present invention was achieved regarding the circumstances describedabove and the problems to be solved by the invention are to provide atherapeutic agent, a kit and a therapeutic method for undifferentiatedgastric cancer, and to provide a pharmaceutical composition, a kit and atherapeutic method which are more effective on a living organismcomprising at least one selected from the group consisting of a celloverexpressing FGFR2 and a cell expressing mutant FGFR2.

In order to solve the above problems, the inventors have gone throughkeen examination, as a result of which the inventors found that acompound represented by General formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof has a FGFR2 inhibitoryactivity. The inventors also found that a compound represented byGeneral formula (I), a pharmacologically acceptable salt thereof or asolvate thereof is more effective on undifferentiated gastric cancer.Furthermore, the inventors found that a compound represented by Generalformula (I), a pharmacologically acceptable salt thereof or a solvatethereof is more effective on a living organism comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2. As a result of further research based onthese findings, the inventors found that a compound represented byGeneral formula (I), a pharmacologically acceptable salt thereof or asolvate thereof has a superior anti-tumor effect when used incombination with a therapeutic substance for gastric cancer as comparedwith that obtained with the therapeutic substance for gastric canceralone in subcutaneous transplanted (xenograft) models (in vivo) of humanscirrhous gastric cancer cell lines. Hence, a FGFR2 inhibitor, forexample, a compound represented by General formula (I), apharmacologically acceptable salt thereof or a solvate thereof appearsto show an excellent anti-tumor effect when used in combination with atherapeutic substance for gastric cancer and thus found that acombination of a FGFR2 inhibitor and a therapeutic substance for gastriccancer may be used as an effective therapeutic agent and kit forundifferentiated gastric cancer, and for undifferentiated gastriccancer.

Thus, the present invention relates to the followings.

(1) A therapeutic agent for undifferentiated gastric cancer comprising acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor.

(2) A pharmaceutical composition for administration to a living organismcomprising at least one selected from the group consisting of a celloverexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising a compound represented by GeneralFormula (I), a pharmacologically acceptable salt thereof or a solvatethereof in combination with a therapeutic substance for gastric canceror a FGFR2 inhibitor.

(3) A method for treating undifferentiated gastric cancer, characterizedby administering effective dosages of a compound represented by GeneralFormula (I), a pharmacologically acceptable salt thereof or a solvatethereof and a therapeutic substance for gastric cancer or a FGFR2inhibitor to a living organism.

(4) A method for treating a disease, characterized by administeringeffective dosages of a compound represented by General Formula (I), apharmacologically acceptable salt thereof or a solvate thereof and atherapeutic substance for gastric cancer or a FGFR2 inhibitor to aliving organism comprising at least one selected from the groupconsisting of a cell overexpressing FGFR2 and a cell expressing mutantFGFR2.

(5) Use of a compound represented by General Formula (I), apharmacologically acceptable salt thereof or a solvate thereof forproducing a therapeutic agent for undifferentiated gastric cancer incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor.

(6) Use of a compound represented by General Formula (I), apharmacologically acceptable salt thereof or a solvate thereof forproducing a pharmaceutical composition in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor for administration toa living organism comprising at least one selected from the groupconsisting of a cell overexpressing FGFR2 and a cell expressing mutantFGFR2.

(7) A compound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof for treatingundifferentiated gastric cancer in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor.

(8) A compound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof for administration incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor to a living organism comprising at least one selected from thegroup consisting of a cell overexpressing FGFR2 and a cell expressingmutant FGFR2.

(9) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor; and

(b) a therapeutic agent for undifferentiated gastric cancer comprising acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof.

(10) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor; and

(b) a pharmaceutical composition comprising a compound represented byGeneral Formula (I), a pharmacologically acceptable salt thereof or asolvate thereof for administration to a living organism comprising atleast one selected from the group consisting of a cell overexpressingFGFR2 and a cell expressing mutant FGFR2.

(11) A kit characterized by a set of a therapeutic agent forundifferentiated gastric cancer comprising a compound represented byGeneral Formula (I), a pharmacologically acceptable salt thereof or asolvate thereof and a formulation comprising a therapeutic substance forgastric cancer or a FGFR2 inhibitor.

(12) A kit used for administration to a living organism comprising atleast one selected from the group consisting of a cell overexpressingFGFR2 and a cell expressing mutant FGFR2, the kit characterized by a setof a formulation comprising a compound represented by General Formula(I), a pharmacologically acceptable salt thereof or a solvate thereofand a formulation comprising a therapeutic substance for gastric canceror a FGFR2 inhibitor.

(13) A therapeutic agent for undifferentiated gastric cancer comprisinga compound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof, characterized byadministration to a living organism with a therapeutic substance forgastric cancer or a FGFR2 inhibitor.

(14) A pharmaceutical composition for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising a compound represented by GeneralFormula (I), a pharmacologically acceptable salt thereof or a solvatethereof, characterized by administration to the living organism with atherapeutic substance for gastric cancer or a FGFR2 inhibitor.

Furthermore, the present invention preferably relates to the followings.

(15) A therapeutic agent for undifferentiated gastric cancer comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor.

(16) A pharmaceutical composition for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor.

(17) A method for treating undifferentiated gastric cancer,characterized by administering effective dosages of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and atherapeutic substance for gastric cancer or a FGFR2 inhibitor to aliving organism.

(18) A method for treating a disease, characterized by administeringeffective dosages of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and atherapeutic substance for gastric cancer or a FGFR2 inhibitor to aliving organism comprising at least one selected from the groupconsisting of a cell overexpressing FGFR2 and a cell expressing mutantFGFR2.

(19) Use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof forproducing a therapeutic agent for undifferentiated gastric cancer incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor.

(20) Use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof forproducing a pharmaceutical composition in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor for administration toa living organism comprising at least one selected from the groupconsisting of a cell overexpressing FGFR2 and a cell expressing mutantFGFR2.

(21)4-(3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof fortreating undifferentiated gastric cancer in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor.

(22)4-(3-Chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof foradministration in combination with a therapeutic substance for gastriccancer or a FGFR2 inhibitor to a living organism comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2.

(23) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor; and

(b) a therapeutic agent for undifferentiated gastric cancer comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof.

(24) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor; and

(b) a pharmaceutical composition comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof foradministration to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2.

(25) A kit characterized by a set of a therapeutic agent forundifferentiated gastric cancer comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and aformulation comprising a therapeutic substance for gastric cancer or aFGFR2 inhibitor.

(26) A kit used for administration to a living organism comprising atleast one selected from the group consisting of a cell overexpressingFGFR2 and a cell expressing mutant FGFR2, the kit characterized by a setof a formulation comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof and aformulation comprising a therapeutic substance for gastric cancer or aFGFR2 inhibitor.

(27) A therapeutic agent for undifferentiated gastric cancer comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof,characterized by administration to a living organism with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor.

(28) A pharmaceutical composition for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,a pharmacologically acceptable salt thereof or a solvate thereof,characterized by administration to the living organism with atherapeutic substance for gastric cancer or a FGFR2 inhibitor.

The present invention also relates to the followings.

(29) A therapeutic agent for undifferentiated gastric cancer comprisinga FGFR2 inhibitor in combination with a therapeutic substance forgastric cancer.

(30) A pharmaceutical composition for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising a FGFR2 inhibitor in combinationwith a therapeutic substance for gastric cancer.

(31) A method for treating undifferentiated gastric cancer,characterized by administering effective dosages of a FGFR2 inhibitorand a therapeutic substance for gastric cancer to a living organism.

(32) A method for treating a disease, characterized by administeringeffective dosages of a FGFR2 inhibitor and a therapeutic substance forgastric cancer to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2.

(33) Use of a FGFR2 inhibitor or a therapeutic substance for gastriccancer for producing a therapeutic agent for undifferentiated gastriccancer in combination with a therapeutic substance for gastric cancer ora FGFR2 inhibitor.

(34) Use of a FGFR2 inhibitor or a therapeutic substance for gastriccancer for producing a pharmaceutical composition in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor foradministration to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2.

(35) A FGFR2 inhibitor or a therapeutic substance for gastric cancer fortreating undifferentiated gastric cancer in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor.

(36) A FGFR2 inhibitor or a therapeutic substance for gastric cancer foradministration in combination with a therapeutic substance for gastriccancer or a FGFR2 inhibitor to a living organism comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2.

(37) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing combinationuse of a FGFR2 inhibitor and a therapeutic substance for gastric cancer;and

(b) a therapeutic agent for undifferentiated gastric cancer comprising aFGFR2 inhibitor or a therapeutic agent for gastric cancer comprising atherapeutic substance for gastric cancer.

(38) A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing combinationuse of a FGFR2 inhibitor and a therapeutic substance for gastric cancer;and

(b) a pharmaceutical composition comprising a FGFR2 inhibitor or atherapeutic substance for gastric cancer for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2.

(39) A kit characterized by a set of a therapeutic agent forundifferentiated gastric cancer comprising a FGFR2 inhibitor and aformulation comprising a therapeutic substance for gastric cancer.

(40) A kit used for administration to a living organism comprising atleast one selected from the group consisting of a cell overexpressingFGFR2 and a cell expressing mutant FGFR2, the kit characterized by a setof a formulation comprising a FGFR2 inhibitor and a formulationcomprising a therapeutic substance for gastric cancer.

(41) A therapeutic agent for undifferentiated gastric cancer comprisinga FGFR2 inhibitor or a therapeutic agent for gastric cancer comprising atherapeutic substance for gastric cancer, characterized byadministration to a living organism with a therapeutic substance forgastric cancer or a FGFR2 inhibitor.

(42) A pharmaceutical composition for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2, thepharmaceutical composition comprising a FGFR2 inhibitor or a therapeuticsubstance for gastric cancer characterized by administration to theliving organism with a therapeutic substance for gastric cancer or aFGFR2 inhibitor.

More specifically, the present invention relates to the followings.

-   [1] A therapeutic agent for undifferentiated gastric cancer    comprising a compound represented by General Formula (I) below, a    pharmacologically acceptable salt thereof or a solvate thereof in    combination with a therapeutic substance for gastric cancer or a    FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [2] A therapeutic agent according to [1], wherein R¹ is a C₁₋₆ alkyl    group (provided that R¹ may have at least one substituent selected    from the group consisting of a 3-10-membered nonaromatic    heterocyclic group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino    group, a mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group    which may have a C₁₋₆ alkyl group).-   [3] A therapeutic agent according to [1], wherein R¹ is a methyl    group or a group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [4] A therapeutic agent according to [1], wherein R¹ is a methyl    group or a 2-methoxyethyl group.-   [5] A therapeutic agent according to [1], wherein R² is a cyano    group or a group represented by Formula —CONV^(a11)V^(a12) (wherein,    V^(a11) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [6] A therapeutic agent according to [1], wherein R² is a cyano    group or a group represented by Formula —CONHV^(a16) (wherein,    V^(a16) represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈    cycloalkyl group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group,    provided that V^(a16) may have at least one substituent selected    from the group consisting of a halogen atom, a cyano group, a    hydroxyl group and a C₁₋₆ alkoxy group).-   [7] A therapeutic agent according to [1], wherein R² is a group    represented by Formula —CONHV^(a17) (wherein, V^(a17) represents a    hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [8] A therapeutic agent according to [1], wherein R² is a group    represented by Formula —CONHV^(a18) (wherein, V^(a18) represents a    hydrogen atom, a methyl group or a methoxy group).-   [9] A therapeutic agent according to [1], wherein Y¹ is a group    represented by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [10] A therapeutic agent according to [1], wherein R³ and R⁴ are    hydrogen atoms.-   [11] A therapeutic agent according to [1], wherein R⁵ is a hydrogen    atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a C₆₋₁₀ aryl    group (provided that R⁵ may have at least one substituent selected    from the group consisting of a halogen atom and a methanesulfonyl    group).-   [12] A therapeutic agent according to [1], wherein R⁵ is a methyl    group, an ethyl group or a cyclopropyl group.-   [13] A therapeutic agent according to [1], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [14] A therapeutic agent according to [1], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [15] A therapeutic agent according to [1], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [16] A therapeutic agent according to [1], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [17] A therapeutic agent according to any one of [1] to [1,6],    wherein the therapeutic substance for gastric cancer is at least one    selected from the group consisting of irinotecan, paclitaxel,    carboquone, nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine,    carmofur, S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin,    epirubicin, docetaxel and cis-platinum.-   [18] A therapeutic agent according to any one of [1] to [1,6],    wherein the therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [19] A therapeutic agent according to any one of [1] to [16],    wherein the FGFR2 inhibitor is at least one compound selected from    the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [20] A therapeutic agent according to [1], wherein the    undifferentiated gastric cancer comprises at least one selected from    the group consisting of a cell overexpressing FGFR2 and a cell    expressing mutant FGFR2.-   [21] A therapeutic agent according to [20], wherein the mutant FGFR2    comprises a mutation site where amino acids downstream from at least    position 813 are deleted in the amino acid sequence 22-822 among the    amino acid sequence represented by SEQ ID NO:2.-   [22] A therapeutic agent according to [1], wherein the    undifferentiated gastric cancer is at least one gastric cancer    selected from the group consisting of poorly differentiated    adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and    scirrhous gastric cancer.-   [23] A pharmaceutical composition for administration to a living    organism comprising at least one selected from the group consisting    of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2,    the pharmaceutical composition comprising a compound represented by    General Formula (I) below, a pharmacologically acceptable salt    thereof or a solvate thereof in combination with a therapeutic    substance for gastric cancer or a FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [24] A pharmaceutical composition according to [23], wherein R¹ is a    C₁₋₆ alkyl group (provided that R¹ may have at least one substituent    selected from the group consisting of a 3-10-membered nonaromatic    heterocyclic group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino    group, a mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group    which may have a C₁₋₆ alkyl group).-   [25] A pharmaceutical composition according to [23], wherein R¹ is a    methyl group or a group represented by any one of the following    formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [26] A pharmaceutical composition according to [23], wherein R¹ is a    methyl group or a 2-methoxyethyl group.-   [27] A pharmaceutical composition according to [23], wherein R² is a    cyano group or a group represented by Formula —CONV^(a11)V^(a12)    (wherein, V^(a11) represents a hydrogen atom, an optionally    substituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenyl    group, an optionally substituted C₂₋₆ alkynyl group, an optionally    substituted C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀    aryl group, an optionally substituted 5-10-membered heteroaryl group    or an optionally substituted 3-10-membered nonaromatic heterocyclic    group; V^(a12) represents a hydrogen atom, an optionally substituted    C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [28] A pharmaceutical composition according to [23], wherein R² is a    cyano group or a group represented by Formula —CONHV^(a16) (wherein,    V^(a16) represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈    cycloalkyl group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group,    provided that V^(a16) may have at least one substituent selected    from the group consisting of a halogen atom, a cyano group, a    hydroxyl group and a C₁₋₆ alkoxy group).-   [29] A pharmaceutical composition according to [23], wherein R² is a    group represented by Formula —CONHV^(a17) (wherein, V^(a17)    represents a hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy    group).-   [30] A pharmaceutical composition according to [23], wherein R² is a    group represented by Formula —CONHV^(a18) (wherein, V^(a18)    represents a hydrogen atom, a methyl group or a methoxy group).-   [31] A pharmaceutical composition according to [23], wherein Y¹ is a    group represented by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [32] A pharmaceutical composition according to [23], wherein R³ and    R⁴ are hydrogen atoms.-   [33] A pharmaceutical composition according to [23], wherein R⁵ is a    hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a    C₆₋₁₀ aryl group (provided that R⁵ may have at least one substituent    selected from the group consisting of a halogen atom and a    methanesulfonyl group).-   [34] A pharmaceutical composition according to [23], wherein R² is a    methyl group, an ethyl group or a cyclopropyl group.-   [35] A pharmaceutical composition according to [23], wherein the    compound represented by General Formula (I), a pharmacologically    acceptable salt thereof or a solvate thereof is at least one    compound selected from the group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [36] A pharmaceutical composition according to [23], wherein the    compound represented by General Formula (I), a pharmacologically    acceptable salt thereof or a solvate thereof is at least one    compound selected from the group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [37] A pharmaceutical composition according to [23], wherein the    compound represented by General Formula (I), a pharmacologically    acceptable salt thereof or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [38] A pharmaceutical composition according to [23], wherein the    compound represented by General Formula (I), a pharmacologically    acceptable salt thereof or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [39] A pharmaceutical composition according to any one of [23] to    [38], wherein the therapeutic substance for gastric cancer is at    least one selected from the group consisting of irinotecan,    paclitaxel, carboquone, nimustine, 5-fluorouracil, tegafur, UFT,    doxifluridine, carmofur, S-1, doxorubicin, mitomycin C, aclarubicin,    pirarubicin, epirubicin, docetaxel and cis-platinum.-   [40] A pharmaceutical composition according to any one of [23] to    [38], wherein the therapeutic substance for gastric cancer is    irinotecan, 5-fluorouracil or paclitaxel.-   [41] A pharmaceutical composition according to any one of [23] to    [38], wherein the FGFR2 inhibitor is at least one compound selected    from the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [42] A pharmaceutical composition according to [23], wherein the    mutant FGFR2 comprises a mutation site where amino acids downstream    from at least position 813 are deleted in the amino acid sequence    22-822 among the amino acid sequence represented by SEQ ID NO:2.-   [43] A pharmaceutical composition according to [23], wherein the    living organism is a patient suffering from undifferentiated gastric    cancer.-   [44] A pharmaceutical composition according to [43], wherein the    undifferentiated gastric cancer is at least one gastric cancer    selected from the group consisting of poorly differentiated    adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and    scirrhous gastric cancer.-   [45] A method for treating undifferentiated gastric cancer,    characterized by administering effective dosages of a compound    represented by General Formula (I) below, a pharmacologically    acceptable salt thereof or a solvate thereof and a therapeutic    substance for gastric cancer or a FGFR2 inhibitor to a living    organism:

[wherein, R⁸ represents a group represented by Formula —V¹—V²V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶— ora group represented by Formula —NR⁶— (wherein, R⁶ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group or an optionallysubstituted C₃₋₈ cycloalkyl group); V³ represents a hydrogen atom, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆alkenyl group, an optionally substituted C₂₋₆ alkynyl group, anoptionally substituted C₃₋₈ cycloalkyl group, an optionally substitutedC₆₋₁₀ aryl group, an optionally substituted 5-10-membered heteroarylgroup or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [46] A therapeutic method according to [45], wherein R¹ is a C₁₋₆    alkyl group (provided that R¹ may have at least one substituent    selected from the group consisting of a 3-10-membered nonaromatic    heterocyclic group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino    group, a mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group    which may have a C₁₋₆ alkyl group).-   [47] A therapeutic method according to [45], wherein R¹ is a methyl    group or a group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [48] A therapeutic method according to [45], wherein R¹ is a methyl    group or a 2-methoxyethyl group.-   [49] A therapeutic method according to [45], wherein R² is a cyano    group or a group represented by Formula —CONV^(a11)V^(a12) (wherein,    V^(a11) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [50] A therapeutic method according to [45], wherein R² is a cyano    group or a group represented by Formula —CONHV^(a16) (wherein,    V^(a16) represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈    cycloalkyl group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group,    provided that V^(a16) may have at least one substituent selected    from the group consisting of a halogen atom, a cyano group, a    hydroxyl group and a C₁₋₆ alkoxy group).-   [51] A therapeutic method according to [45], wherein R² is a group    represented by Formula —CONHV^(a17) (wherein, V^(a17) represents a    hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [52] A therapeutic method according to [45], wherein R² is a group    represented by Formula —CONHV^(a18) (wherein, V^(a18) represents a    hydrogen atom, a methyl group or a methoxy group).-   [53] A therapeutic method according to [45], wherein Y¹ is a group    represented by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [54] A therapeutic method according to [45], wherein R³ and R⁴ are    hydrogen atoms.-   [55] A therapeutic method according to [45], wherein R⁵ is a    hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a    C₆₋₁₀ aryl group (provided that R⁵ may have at least one substituent    selected from the group consisting of a halogen atom and a    methanesulfonyl group).-   [56] A therapeutic method according to [45], wherein R⁵ is a methyl    group, an ethyl group or a cyclopropyl group.-   [57] A therapeutic method according to [45], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [58] A therapeutic method according to [45], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [59] A therapeutic method according to [45], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [60] A therapeutic method according to [45], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [61] A therapeutic method according to any one of [45] to [60],    wherein the therapeutic substance for gastric cancer is at least one    selected from the group consisting of irinotecan, paclitaxel,    carboquone, nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine,    carmofur, S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin,    epirubicin, docetaxel and cis-platinum.-   [62] A therapeutic method according to any one of [45] to [60],    wherein the therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [63] A therapeutic method according to any one of [45] to [60],    wherein the FGFR2 inhibitor is at least one compound selected from    the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [64] A therapeutic method according to [45], wherein the mutant    FGFR2 comprises a mutation site where amino acids downstream from at    least position 813 are deleted in the amino acid sequence 22-822    among the amino acid sequence represented by SEQ ID NO:2.-   [65] A therapeutic method according to [45], wherein the living    organism is a patient suffering from undifferentiated gastric    cancer.-   [66] A therapeutic method according to [65], wherein the    undifferentiated gastric cancer is at least one gastric cancer    selected from the group consisting of poorly differentiated    adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and    scirrhous gastric cancer.-   [67] A method for treating a disease, characterized by administering    effective dosages of a compound represented by General Formula (I)    below, a pharmacologically acceptable salt thereof or a solvate    thereof and a therapeutic substance for gastric cancer or a FGFR2    inhibitor to a living organism comprising at least one selected from    the group consisting of a cell overexpressing FGFR2 and a cell    expressing mutant FGFR2:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [68] A therapeutic method according to [67], wherein R¹ is a C₁₋₆    alkyl group (provided that R¹ may have at least one substituent    selected from the group consisting of a 3-10-membered nonaromatic    heterocyclic group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino    group, a mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group    which may have a C₁₋₆ alkyl group).-   [69] A therapeutic method according to [67], wherein R¹ is a methyl    group or a group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [70] A therapeutic method according to [67], wherein R¹ is a methyl    group or a 2-methoxyethyl group.-   [71] A therapeutic method according to [67], wherein R² is a cyano    group or a group represented by Formula —CONV^(a11)V^(a12) (wherein,    V^(a11) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [72] A therapeutic method according to [67], wherein R² is a cyano    group or a group represented by Formula —CONHV^(a16) (wherein,    V^(a16) represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈    cycloalkyl group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group,    provided that V^(a16) may have at least one substituent selected    from the group consisting of a halogen atom, a cyano group, a    hydroxyl group and a C₁₋₆ alkoxy group).-   [73] A therapeutic method according to [67], wherein R² is a group    represented by Formula —CONHV^(a17) (wherein, V^(a17) represents a    hydrogen atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [74] A therapeutic method according to [67], wherein R² is a group    represented by Formula —CONHV^(a18) (wherein, V^(a18) represents a    hydrogen atom, a methyl group or a methoxy group).-   [75] A therapeutic method according to [67], wherein Y¹ is a group    represented by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [76] A therapeutic method according to [67], wherein R³ and R⁴ are    hydrogen atoms.-   [77] A therapeutic method according to [67], wherein R⁵ is a    hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a    C₆₋₁₀ aryl group (provided that R⁵ may have at least one substituent    selected from the group consisting of a halogen atom and a    methanesulfonyl group).-   [78] A therapeutic method according to [67], wherein R⁵ is a methyl    group, an ethyl group or a cyclopropyl group.-   [79] A therapeutic method according to [67], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [80] A therapeutic method according to [67], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is at least one compound selected    from the group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [81] A therapeutic method according to [67], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [82] A therapeutic method according to [67], wherein the compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [83] A therapeutic method according to any one of [67] to [82],    wherein the therapeutic substance for gastric cancer is at least one    selected from the group consisting of irinotecan, paclitaxel,    carboquone, nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine,    carmofur, S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin,    epirubicin, docetaxel and cis-platinum.-   [84] A therapeutic method according to any one of [67] to [82],    wherein the therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [85] A therapeutic method according to any one of [67] to [82],    wherein the FGFR2 inhibitor is at least one compound selected from    the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]    indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [86] A therapeutic method according to [67], wherein the mutant    FGFR2 comprises a mutation site where amino acids downstream from at    least position 813 are deleted in the amino acid sequence 22-822    among the amino acid sequence represented by SEQ ID NO:2.-   [87] A therapeutic method according to [67], wherein the living    organism is a patient suffering from undifferentiated gastric    cancer.-   [88] A therapeutic method according to [87], wherein the    undifferentiated gastric cancer is at least one gastric cancer    selected from the group consisting of poorly differentiated    adenocarcinoma, signet-ring cell carcinoma, mucinous carcinoma and    scirrhous gastric cancer.-   [89] Use of a compound represented by General Formula (I) below, a    pharmacologically acceptable salt thereof or a solvate thereof for    producing a therapeutic agent for undifferentiated gastric cancer in    combination with a therapeutic substance for gastric cancer or a    FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [90 Use according to [89], wherein R¹ is a C₁₋₆ alkyl group    (provided that R¹ may have at least one substituent selected from    the group consisting of a 3-10-membered nonaromatic heterocyclic    group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino group, a    mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group which may    have a C₁₋₆ alkyl group).-   [91] Use according to [89], wherein R¹ is a methyl group or a group    represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [92] Use according to [89], wherein R¹ is a methyl group or a    2-methoxyethyl group.-   [93] Use according to [89], wherein R² is a cyano group or a group    represented by Formula —CONV^(a11)V^(a12) (wherein, V^(a11)    represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [94] Use according to [89], wherein R² is a cyano group or a group    represented by Formula —CONHV^(a16) (wherein, V^(a16) represents a    hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group, a C₁₋₆    alkoxy group or a C₃₋₈ cycloalkoxy group, provided that V^(a16) may    have at least one substituent selected from the group consisting of    a halogen atom, a cyano group, a hydroxyl group and a C₁₋₆ alkoxy    group).-   [95] Use according to [89], wherein R² is a group represented by    Formula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen atom, a    C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [96] Use according to [89], wherein R² is a group represented by    Formula —CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, a    methyl group or a methoxy group).-   [97] Use according to [89], wherein Y¹ is a group represented by the    following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [98] Use according to [89], wherein R³ and R⁴ are hydrogen atoms.-   [99] Use according to [89], wherein R⁵ is a hydrogen atom, a C₁₋₆    alkyl group, a C₃₋₈ cycloalkyl group or a C₆₋₁₀ aryl group (provided    that R⁵ may have at least one substituent selected from the group    consisting of a halogen atom and a methanesulfonyl group).-   [100] Use according to [89], wherein R⁵ is a methyl group, an ethyl    group or a cyclopropyl group.-   [101] Use according to [89], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is at least one compound selected from the group    consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [102] Use according to [89], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is at least one compound selected from the group    consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [103] Use according to [89], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [104] Use according to [89], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [105] Use according to any one of [89] to [104], wherein the    therapeutic substance for gastric cancer is at least one selected    from the group consisting of irinotecan, paclitaxel, carboquone,    nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine, carmofur,    S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin, epirubicin,    docetaxel and cis-platinum.-   [106] Use according to any one of [89] to [104], wherein the    therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [107] Use according to any one of [89] to [104], wherein the FGFR2    inhibitor is at least one compound selected from the group    consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [108] Use according to [89], wherein the undifferentiated gastric    cancer comprises at least one selected from the group consisting of    a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.-   [109] Use according to [108], wherein the mutant FGFR2 comprises a    mutation site where amino acids downstream from at least position    813 are deleted in the amino acid sequence 22-822 among the amino    acid sequence represented by SEQ ID NO:2.-   [110] Use according to [89], wherein the undifferentiated gastric    cancer is at least one gastric cancer selected from the group    consisting of poorly differentiated adenocarcinoma, signet-ring cell    carcinoma, mucinous carcinoma and scirrhous gastric cancer.-   [111] Use of a compound represented by General Formula (I) below, a    pharmacologically acceptable salt thereof or a solvate thereof for    producing a pharmaceutical composition in combination with a    therapeutic substance for gastric cancer or a FGFR2 inhibitor for    administration to a living organism comprising at least one selected    from the group consisting of a cell overexpressing FGFR2 and a cell    expressing mutant FGFR2:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [112] Use according to [111], wherein R¹ is a C₁₋₆ alkyl group    (provided that R¹ may have at least one substituent selected from    the group consisting of a 3-10-membered nonaromatic heterocyclic    group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino group, a    mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group which may    have a C₁₋₆ alkyl group).-   [113] Use according to [111], wherein R¹ is a methyl group or a    group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [114] Use according to [111], wherein R¹ is a methyl group or a    2-methoxyethyl group.-   [115] Use according to [111], wherein R² is a cyano group or a group    represented by Formula —CONV^(a11)V^(a12) (wherein, V^(a11)    represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [116] Use according to [111], wherein R² is a cyano group or a group    represented by Formula —CONHV^(a16) (wherein, V^(a16) represents a    hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group, a C₁₋₆    alkoxy group or a C₃₋₈ cycloalkoxy group, provided that V^(a16) may    have at least one substituent selected from the group consisting of    a halogen atom, a cyano group, a hydroxyl group and a C₁₋₆ alkoxy    group).-   [117] Use according to [111], wherein R² is a group represented by    Formula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen atom, a    C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [118] Use according to [111], wherein R² is a group represented by    Formula —CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, a    methyl group or a methoxy group).-   [119] Use according to [111], wherein Y¹ is a group represented by    the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [120] Use according to [111], wherein R³ and R⁴ are hydrogen atoms.-   [121] Use according to [111], wherein R⁵ is a hydrogen atom, a C₁₋₆    alkyl group, a C₃₋₈ cycloalkyl group or a C₆₋₁₀ aryl group (provided    that R⁵ may have at least one substituent selected from the group    consisting of a halogen atom and a methanesulfonyl group).-   [122] Use according to [111], wherein R⁵ is a methyl group, an ethyl    group or a cyclopropyl group.-   [123] Use according to [111], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is at least one compound selected from the group    consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [124] Use according to [111], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is at least one compound selected from the group    consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [125] Use according to [111], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [126] Use according to [111], wherein the compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [127] Use according to any one of [111] to [116], wherein the    therapeutic substance for gastric cancer is at least one selected    from the group consisting of irinotecan, paclitaxel, carboquone,    nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine, carmofur,    S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin, epirubicin,    docetaxel and cis-platinum.-   [128] Use according to any one of [111] to [116], wherein the    therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [129] Use according to any one of [111] to [116], wherein the FGFR2    inhibitor is at least one compound selected from the group    consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [130] Use according to [111], wherein the undifferentiated gastric    cancer comprises at least one selected from the group consisting of    a cell overexpressing FGFR2 and a cell expressing mutant FGFR2.-   [131] Use according to [130], wherein the mutant FGFR2 comprises a    mutation site where amino acids downstream from at least position    813 are deleted in the amino acid sequence 22-822 among the amino    acid sequence represented by SEQ ID NO:2.-   [132] Use according to [111], wherein the undifferentiated gastric    cancer is at least one gastric cancer selected from the group    consisting of poorly differentiated adenocarcinoma, signet-ring cell    carcinoma, mucinous carcinoma and scirrhous gastric cancer.-   [133] A compound represented by General Formula (I) below, a    pharmacologically acceptable salt thereof or a solvate thereof for    treating undifferentiated gastric cancer in combination with a    therapeutic substance for gastric cancer or a FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresentes by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [134] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a C₁₋₆ alkyl group    (provided that R¹ may have at least one substituent selected from    the group consisting of a 3-10-membered nonaromatic heterocyclic    group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino group, a    mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group which may    have a C₁₋₆ alkyl group).-   [135] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a methyl group or a    group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [136] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a methyl group or a    2-methoxyethyl group.-   [137] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a cyano group or a    group represented by Formula —CONV^(a11)V^(a12) (wherein, V^(a11)    represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [138] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a cyano group or a    group represented by Formula —CONHV^(a16) (wherein, V^(a16)    represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl    group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group, provided    that V^(a16) may have at least one substituent selected from the    group consisting of a halogen atom, a cyano group, a hydroxyl group    and a C₁₋₆ alkoxy group).-   [139] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a group represented    by Formula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen    atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [140] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a group represented    by Formula —CONHV^(a18) (wherein, V^(a18) represents a hydrogen    atom, a methyl group or a methoxy group).-   [141] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein Y¹ is a group represented    by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [142] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R³ and R⁴ are hydrogen    atoms.-   [143] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R⁵ is a hydrogen atom, a    C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a C₆₋₁₀ aryl group    (provided that R⁵ may have at least one substituent selected from    the group consisting of a halogen atom and a methanesulfonyl group).-   [144] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R⁵ is a methyl group, an    ethyl group or a cyclopropyl group.-   [145] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is at least one compound selected from the    group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [146] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is at least one compound selected from the    group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [147] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [148] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [149] A compound according to any one of [133] to [148], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the therapeutic substance for gastric cancer is at least one    selected from the group consisting of irinotecan, paclitaxel,    carboquone, nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine,    carmofur, S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin,    epirubicin, docetaxel and cis-platinum.-   [150] A compound according to any one of [133] to [148], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [151] A compound according to any one of [133] to [148], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the FGFR2 inhibitor is at least one compound selected from    the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [152] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the undifferentiated    gastric cancer comprises at least one selected from the group    consisting of a cell overexpressing FGFR2 and a cell expressing    mutant FGFR2.-   [153] A compound according to [152], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the mutant FGFR2    comprises a mutation site where amino acids downstream from at least    position 813 are deleted in the amino acid sequence 22-822 among the    amino acid sequence represented by SEQ ID NO:2.-   [154] A compound according to [133], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the undifferentiated    gastric cancer is at least one gastric cancer selected from the    group consisting of poorly differentiated adenocarcinoma,    signet-ring cell carcinoma, mucinous carcinoma and scirrhous gastric    cancer.-   [155] A compound represented by General Formula (I) below, a    pharmacologically acceptable salt thereof or a solvate thereof for    administration in combination with a therapeutic substance for    gastric cancer or a FGFR2 inhibitor to a living organism comprising    at least one selected from the group consisting of a cell    overexpressing FGFR2 and a cell expressing mutant FGFR2:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [156] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a C₁₋₆ alkyl group    (provided that R¹ may have at least one substituent selected from    the group consisting of a 3-10-membered nonaromatic heterocyclic    group, a hydroxyl group, a C₁₋₆ alkoxy group, an amino group, a    mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group which may    have a C₁₋₆ alkyl group).-   [157] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a methyl group or a    group represented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

-   [158] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R¹ is a methyl group or a    2-methoxyethyl group.-   [159] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a cyano group or a    group represented by Formula —CONV^(a11)V^(a12) (wherein, V^(a11)    represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic group;    V^(a12) represents a hydrogen atom, an optionally substituted C₁₋₆    alkyl group, an optionally substituted C₂₋₆ alkenyl group, an    optionally substituted C₂₋₆ alkynyl group, an optionally substituted    C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group,    an optionally substituted 5-10-membered heteroaryl group, an    optionally substituted 3-10-membered nonaromatic heterocyclic group,    a hydroxyl group, an optionally substituted C₁₋₆ alkoxy group or an    optionally substituted C₃₋₈ cycloalkoxy group).-   [160] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a cyano group or a    group represented by Formula —CONHV^(a16) (wherein, V^(a16)    represents a hydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl    group, a C₁₋₆ alkoxy group or a C₃₋₈ cycloalkoxy group, provided    that V^(a16) may have at least one substituent selected from the    group consisting of a halogen atom, a cyano group, a hydroxyl group    and a C₁₋₆ alkoxy group).-   [161] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a group represented    by Formula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen    atom, a C₁₋₆ alkyl group or a C₁₋₆ alkoxy group).-   [162] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R² is a group represented    by Formula —CONHV^(a18) (wherein, V^(a18) represents a hydrogen    atom, a methyl group or a methoxy group).-   [163] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein Y¹ is a group represented    by the following formula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

-   [164] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R³ and R⁴ are hydrogen    atoms.-   [165] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R⁵ is a hydrogen atom, a    C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group or a C₆₋₁₀ aryl group    (provided that R⁵ may have at least one substituent selected from    the group consisting of a halogen atom and a methanesulfonyl group).-   [166] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein R⁵ is a methyl group, an    ethyl group or a cyclopropyl group.-   [167] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is at least one compound selected from the    group consisting of:-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [168] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is at least one compound selected from the    group consisting of:-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [169] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [170] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the compound represented    by General Formula (I), a pharmacologically acceptable salt thereof    or a solvate thereof is methanesulfonate of    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.-   [171] A compound according to any one of [155] to [170], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the therapeutic substance for gastric cancer is at least one    selected from the group consisting of irinotecan, paclitaxel,    carboquone, nimustine, 5-fluorouracil, tegafur, UFT, doxifluridine,    carmofur, S-1, doxorubicin, mitomycin C, aclarubicin, pirarubicin,    epirubicin, docetaxel and cis-platinum.-   [172] A compound according to any one of [155] to [170], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the therapeutic substance for gastric cancer is irinotecan,    5-fluorouracil or paclitaxel.-   [173] A compound according to any one of [155] to [170], a    pharmacologically acceptable salt thereof or a solvate thereof,    wherein the FGFR2 inhibitor is at least one compound selected from    the group consisting of:-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea;-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole;-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide; and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea,    a pharmacologically acceptable salt thereof or a solvate thereof.-   [174] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the undifferentiated    gastric cancer comprises at least one selected from the group    consisting of a cell overexpressing FGFR2 and a cell expressing    mutant FGFR2.-   [175] A compound according to [174], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the mutant FGFR2    comprises a mutation site where amino acids downstream from at least    position 813 are deleted in the amino acid sequence 22-822 among the    amino acid sequence represented by SEQ ID NO:2.-   [176] A compound according to [155], a pharmacologically acceptable    salt thereof or a solvate thereof, wherein the undifferentiated    gastric cancer is at least one gastric cancer selected from the    group consisting of poorly differentiated adenocarcinoma,    signet-ring cell carcinoma, mucinous carcinoma and scirrhous gastric    cancer.-   [177] A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor; and

(b) a therapeutic agent for undifferentiated gastric cancer comprising acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [178] A kit comprising:

(a) at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing use of acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor; and

(b) a pharmaceutical composition comprising a compound represented byGeneral Formula (I), a pharmacologically acceptable salt thereof or asolvate thereof for administration to a living organism comprising atleast one selected from the group consisting of a cell overexpressingFGFR2 and a cell expressing mutant FGFR2:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [179] A kit characterized by a set of a therapeutic agent for    undifferentiated gastric cancer comprising a compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof and a formulation comprising a therapeutic    substance for gastric cancer or a FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [180] A kit used for administration to a living organism comprising    at least one selected from the group consisting of a cell    overexpressing FGFR2 and a cell expressing mutant FGFR2, the kit    characterized by a set of a formulation comprising a compound    represented by General Formula (I), a pharmacologically acceptable    salt thereof or a solvate thereof and a formulation comprising a    therapeutic substance for gastric cancer or a FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [181] A therapeutic agent for undifferentiated gastric cancer    comprising a compound represented by General Formula (I), a    pharmacologically acceptable salt thereof or a solvate thereof    characterized by administration to a living organism with a    therapeutic substance for gastric cancer or a FGFR2 inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].-   [182] A pharmaceutical composition for administration to a living    organism comprising at least one selected from the group consisting    of a cell overexpressing FGFR2 and a cell expressing mutant FGFR2,    the pharmaceutical composition comprising a compound represented by    General Formula (I), a pharmacologically acceptable salt thereof or    a solvate thereof characterized by administration to the living    organism with a therapeutic substance for gastric cancer or a FGFR2    inhibitor:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);-   Y¹ represents a group represented by either one of the following    formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group].

According to (1) to (42) and [1] to [182] above, a compound representedby General Formula (I), a pharmacologically acceptable salt thereof or asolvate thereof is as follows. A compound represented by:

[wherein, R¹ represents a group represented by Formula —V¹—V²—V³(wherein, V¹ represents an optionally substituted C₁₋₆ alkylene group;V² represents a single bond, an oxygen atom, a sulfur atom, a carbonylgroup, a sulfinyl group, a sulfonyl group, a group represented byFormula —CONR⁶—, a group represented by Formula —SO₂NR⁶—, a grouprepresented by Formula —NR⁶SO₂—, a group represented by Formula —NR⁶CO—or a group represented by Formula —NR⁶— (wherein, R⁶ represents ahydrogen atom, an optionally substituted C₁₋₆ alkyl group or anoptionally substituted C₃₋₈ cycloalkyl group); V³ represents a hydrogenatom, an optionally substituted C₁₋₆ alkyl group, an optionallysubstituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynylgroup, an optionally substituted C₃₋₈ cycloalkyl group, an optionallysubstituted C₆₋₁₀ aryl group, an optionally substituted 5-10-memberedheteroaryl group or an optionally substituted 3-10-membered nonaromaticheterocyclic group);

-   R² represents a cyano group, an optionally substituted C₁₋₆ alkoxy    group, a carboxyl group, an optionally substituted C₂₋₇    alkoxycarbonyl group or a group represented by Formula    —CONV^(a11)V^(a12) (wherein, V^(a11) represents a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₆₋₁₀ aryl group, an optionally substituted    5-10-membered heteroaryl group or an optionally substituted    3-10-membered nonaromatic heterocyclic group; V^(a12) represents a    hydrogen atom, an optionally substituted C₁₋₆ alkyl group, an    optionally substituted C₂₋₆ alkenyl group, an optionally substituted    C₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group,    an optionally substituted C₆₋₁₀ aryl group, an optionally    substituted 5-10-membered heteroaryl group, an optionally    substituted 3-10-membered nonaromatic heterocyclic group, a hydroxyl    group, an optionally substituted C₁₋₆ alkoxy group or an optionally    substituted C₃₋₈ cycloalkoxy group);    -   Y¹ represents a group represented by either one of the following        formulae

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);

-   W¹ and W² each independently represent an optionally substituted    carbon atom or nitrogen atom);-   R³ and R⁴ each independently represent a hydrogen atom, an    optionally substituted C₁₋₆ alkyl group, an optionally substituted    C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an    optionally substituted C₃₋₈ cycloalkyl group, an optionally    substituted C₂₋₇ acyl group or an optionally substituted C₂₋₇    alkoxycarbonyl group; and-   R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl    group, an optionally substituted C₂₋₆ alkenyl group, an optionally    substituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈    cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, an    optionally substituted 5-10-membered heteroaryl group or an    optionally substituted 3-10-membered nonaromatic heterocyclic    group],    a pharmacologically acceptable salt thereof or a solvate thereof.

Furthermore, according to (1) to (42) above, the therapeutic substancefor gastric cancer may be at least one selected from the groupconsisting of irinotecan, paclitaxel, carboquone, nimustine,5-fluorouracil, tegafur, UFT, doxifluridine, carmofur, S-1, doxorubicin(Adriamycin), mitomycin C, aclarubicin, pirarubicin, epirubicin,docetaxel and cis-platinum (Cisplastin). A preferable therapeuticsubstance for gastric cancer is irinotecan, 5-fluorouracil orpaclitaxel.

Moreover, according to (1) to (42) above, the FGFR2 inhibitor maycomprise, for example, a compound that is not comprised in compoundsrepresented by General Formula (I), and may include at least onecompound selected from the group consisting of:

-   N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea    (BAY 43-9006);-   6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole    (AG013736);-   5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic    acid(2-diethylaminoethyl)amide (SU11248); and-   N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea    (KRN951),    a pharmacologically acceptable salt thereof or a solvate thereof.

The present invention provides a therapeutic agent, a kit and atherapeutic method for undifferentiated gastric cancer that show anexcellent anti-tumor activity, use of a FGFR2 inhibitor for producingthe therapeutic agent and a FGFR2 inhibitor for the therapeutic agent.

More specifically, there is provided a therapeutic agent, a kit and atherapeutic method for undifferentiated gastric cancer that show anexcellent anti-tumor activity and that can be used for treatingundifferentiated gastric cancer by combining:

(i) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a therapeutic substance for gastric cancer;

(ii) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a FGFR2 inhibitor that is not comprised in the compoundsrepresented by General Formula (I); or

(iii) a FGFR2 inhibitor such as a FGFR2 inhibitor that is not comprisedin the compounds represented by General Formula (I) and a therapeuticsubstance for gastric cancer.

The present invention also provides a pharmaceutical composition and akit for administration to a living organism comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2, a method for treating a disease of theliving organism, use of a FGFR2 inhibitor for producing thepharmaceutical composition and a FGFR2 inhibitor for the pharmaceuticalcomposition.

More specifically, there is provided a pharmaceutical composition, a kitand a therapeutic method for the living organism, which show anexcellent anti-tumor activity and that can be used for treating adisease by combining:

(i) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a therapeutic substance for gastric cancer;

(ii) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a FGFR2 inhibitor that is not comprised in the compoundsrepresented by General Formula (I); or

(iii) a FGFR2 inhibitor such as a FGFR2 inhibitor that is not comprisedin the compounds represented by General Formula (I) and a therapeuticsubstance for gastric cancer.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (3 mg/kg) and irinotecan hydrochloride (100 mg/kg) onsuppression of tumor growth in subcutaneous transplanted (xenograft)models (in vivo) of human scirrhous gastric cancer cell line (HSC-39).

FIG. 2 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (10 mg/kg) and irinotecan hydrochloride (100 mg/kg) onsuppression of tumor growth in subcutaneous transplanted (xenograft)models (in vivo) of human scirrhous gastric cancer cell line (HSC-39).

FIG. 3 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (30 mg/kg) and irinotecan hydrochloride (100 mg/kg) onsuppression of tumor growth in subcutaneous transplanted (xenograft)models (in vivo) of human scirrhous gastric cancer cell line (HSC-39).

FIG. 4 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (3 mg/kg) and 5-fluorouracil (50 mg/kg) on suppression oftumor growth in subcutaneous transplanted (xenograft) models (in vivo)of human scirrhous gastric cancer cell line (HSC-39).

FIG. 5 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (10 mg/kg) and 5-fluorouracil (50 mg/kg) on suppression oftumor growth in subcutaneous transplanted (xenograft) models (in vivo)of human scirrhous gastric cancer cell line (HSC-39).

FIG. 6 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (30 mg/kg) and 5-fluorouracil (50 mg/kg) on suppression oftumor growth in subcutaneous transplanted (xenograft) models (in vivo)of human scirrhous gastric cancer cell line (HSC-39).

FIG. 7 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (3 mg/kg) and paclitaxel (14 mg/kg) on suppression of tumorgrowth in subcutaneous transplanted (xenograft) models (in vivo) ofhuman scirrhous gastric cancer cell line (HSC-39).

FIG. 8 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (10 mg/kg) and paclitaxel (14 mg/kg) on suppression oftumor growth in subcutaneous transplanted (xenograft) models (in vivo)of human scirrhous gastric cancer cell line (HSC-39).

FIG. 9 shows the effect of combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) (30 mg/kg) and paclitaxel (14 mg/kg) on suppression oftumor growth in subcutaneous transplanted (xenograft) models (in vivo)of human scirrhous gastric cancer cell line (HSC-39).

BEST MODES FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described. Thefollowing embodiments are examples provided for illustrating the presentinvention, and the present invention is not intended to be limitedthereto. The present invention may be carried out in various embodimentswithout departing from the spirit of the invention.

The publications, laid-open patent publications, patent publications andother patent documents cited herein are incorporated herein byreference. The present specification incorporates the disclosure of U.S.provisional application No. 60/887,006 (filed on 29 Jan., 2007) based onwhich the present application claims priority.

1. FGFR2 Inhibitor

(1) FGFR2

According to the present invention, FGFR2 comprises a polypeptideincluding an amino acid sequence identical or substantially identical tothe amino acid sequence represented by SEQ ID NO:2 (GenBank AccessionNo:NM_(—)022970) or to the amino acids 22-822 of the amino acid sequencerepresented by SEQ ID NO:2. The polypeptide including the amino acidsequence represented by SEQ ID NO:2 is coded, for example, by apolynucleotide including the base sequence represented by SEQ ID NO:1.Usually, processing of the polypeptide comprising the amino acidsequence represented by SEQ ID NO:2 yields a mature form.

Examples of a polypeptide having an amino acid sequence substantiallyidentical to the amino acid sequence (amino acids 22-822) represented bySEQ ID NO:2 include those selected from the group consisting of (a) to(d) below:

(a) a polypeptide comprising the amino acid sequence (amino acids22-822) represented by SEQ ID NO:2;

(b) a polypeptide comprising an amino acid sequence having one or more(e.g., one or a few) amino acids deleted, substituted or added, ormutated by a combination thereof in the amino acid sequence (amino acids22-822) represented by SEQ ID NO:2, and having substantially the sameactivity as FGFR2;

(c) a polypeptide encoded by a polynucleotide that hybridizes with apolynucleotide having a base sequence complementary to the base sequencerepresented by SEQ ID NO: 1 under stringent conditions, and havingsubstantially the same activity as FGFR2; and

(d) a polypeptide having an amino acid sequence having 90% or higher,preferably about 95% or higher and more preferably about 98% or higheridentity (also referred to as “homology”) to the amino acid sequence(amino acids 22-822) represented by SEQ ID NO:2, and havingsubstantially the same activity as FGFR2.

Herein, the phrase “having substantially the same activity as FGFR2”means that at least one of the intracellular signals caused by ligand(e.g., FGF) binding is identical to one of the signals of a proteinhaving the amino acid sequence (amino acids 22-822) represented by SEQID NO:2, and that the activation level of the intracellular signal iscomparable to that of the protein having the amino acid sequence (aminoacids 22-822) represented by SEQ ID NO:2. Furthermore, the term“comparable” means, for example, that the activation level of theintracellular signal caused by ligand (e.g., FGF) binding is at least10%, preferably at least 30% of the activation level of theintracellular signal of a protein having the amino acid sequence (aminoacids 22-822) represented by SEQ ID NO:2, which can be referred to assubstantially the same activity. Examples of intracellular signalscaused by ligand binding include: FGFR2 phosphorylation; Raf, MEK, ERK1and ERK2 phosphorylation owing to FGFR2 phosphorylation; phosphorylationof phosphatidylinositol 3 kinase; Akt phosphorylation; phosphorylationof phospholipase-C-γ; increase in inositol 1,4,5-trisphosphate (IP3);and increase in diacylglycerol (DAG).

The activity of an intracellular signal caused by ligand binding can bemeasured by a conventional method such as immunoprecipitation method andwestern blotting.

Examples of amino acid sequences having one or more (e.g., one or a few)amino acids deleted, substituted or added, or mutated by a combinationthereof in the amino acid sequence (amino acids 22-822) represented bySEQ ID NO:2 include:

(i) an amino acid sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) amino acids deleted fromthe amino acid sequence (amino acids 22-822) represented by SEQ ID NO:2;

(ii) an amino acid sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) amino acids added to theamino acid sequence (amino acids 22-822) represented by SEQ ID NO:2;

(iii) an amino acid sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) amino acids substitutedwith other amino acids in the amino acid sequence (amino acids 22-822)represented by SEQ ID NO:2; and

(iv) an amino acid sequence mutated by a combination of (i) to (iii)above.

As used herein, “deletion” of an amino acid refers to a mutation whereone or more amino acid residues in the sequence are deleted, includingdeletion of amino acid residues from the end of the amino acid sequenceand deletion in the middle of the amino acid sequence.

As used herein, “addition” of an amino acid refers to a mutation whereone or more amino acid residues are added to the sequence, includingaddition of amino acid residues to the end of the amino acid sequenceand addition in the middle of the amino acid sequence. Addition in themiddle of the sequence may also be referred to as “insertion”.

As used herein, “substitution” of an amino acid refers to a mutationwhere one or more amino acid residues in the sequence are substitutedwith different types of amino acid residues. When the amino acidsequence of FGFR2 is modified by such substitution, conservativesubstitution is preferable in order to retain the function of a protein.Conservative substitution means to alter a sequence to code an aminoacid having similar property to the original amino acid. The property ofamino acids can be classified, for example, into nonpolar amino acids(Ala, Ile, Leu, Met, Phe, Pro, Trp, Val), uncharged amino acids (Asn,Cys, Gln, Gly, Ser, Thr, Tyr), acidic amino acids (Asp, Glu), basicamino acids (Arg, His, Lys), neutral amino acids (Ala, Asn, Cys, Gln,Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val), aliphatic aminoacids (Ala, Gly), branched amino acids (Ile, Leu, Val), hydroxyaminoacids (Ser, Thr), amide amino acids (Gln, Asn), sulfur-containing aminoacids (Cys, Met), aromatic amino acids (His, Phe, Trp, Tyr),heterocyclic amino acids (His, Trp), imino acids (Pro, 4Hyp) and thelike.

Thus, substitution, for example, between nonpolar amino acids or betweenuncharged amino acids, is preferable, among which, substitutions betweenAla, Val, Leu and Ile, between Ser and Thr, between Asp and Glu, betweenAsn and Gln, between Lys and Arg, and between Phe and Tyr are favorableas substitution that retains the property of the protein. There is nolimitation as to the number and the site of the amino acid to bemutated.

An example of a polypeptide having substantially the same amino acidsequence as the amino acid sequence (amino acids 22-822) represented bySEQ ID NO:2 includes a polypeptide encoded by a polynucleotide thathybridizes with a polynucleotide having a base sequence complementary tothe base sequence represented by SEQ ID NO:1 under stringent conditions,and having substantially the same activity as FGFR2 as described above.

Herein, specific examples of polynucleotides that hybridize understringent conditions include polynucleotides including base sequenceshaving at least 90% or higher, preferably 95% or higher, more preferably97% or higher, more preferably 98% or higher, or still more preferably99% or higher identity with the base sequence represented by SEQ ID NO:1when calculated using homology search software such as FASTA, BLAST,Smith-Waterman [Meth. Enzym., 164, 765 (1988)] with default (initialsetting) parameters. Examples of such stringent conditions include“2×SSC, 0.1% SDS, 50° C.”, “2×SSC, 0.1% SDS, 42° C.,” and “1×SSC, 0.1%SDS, 37° C.”, and for higher stringent conditions “2×SSC, 0.1% SDS, 65°C.,” “0.5×SSC, 0.1% SDS, 42° C.,” and “0.2×SSC, 0.1% SDS, 65° C.”.

Hybridization can be carried out according to a known method. When acommercially available library is used, hybridization may be carried outaccording to the method described in the attached instruction.

Examples of polynucleotides that hybridize with a polynucleotide havinga base sequence complementary to the base sequence represented by SEQ IDNO:1 under stringent conditions include polynucleotides comprising abase sequence having 90% or higher, preferably 95% or higher and morepreferably 98% or higher identity with the base sequence represented bySEQ ID NO:1.

Examples of polynucleotides that hybridize with a polynucleotide havinga base sequence complementary to the base sequence represented by SEQ IDNO:1 under stringent conditions include base sequences having one ormore (e.g., one or several) nucleic acids mutated, for example, deleted,substituted or added in the base sequence represented by SEQ ID NO:1.

Examples of polynucleotides that hybridize with a polynucleotide havinga base sequence complementary to the base sequence represented by SEQ IDNO:1 under stringent conditions include:

(i) a base sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) nucleic acids deleted fromthe base sequence represented by SEQ ID NO:1;

(ii) a base sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) nucleic acids added to thebase sequence represented by SEQ ID NO:1;

(iii) a base sequence having 1-9 (e.g., 1-5, preferably 1-3, morepreferably 1-2 and still more preferably one) nucleic acids substitutedwith other nucleic acids in the base sequence represented by SEQ IDNO:1; and

(iv) a base sequence mutated by a combination of (i) to (iii) above.

Herein, the term “identity” (also referred to as “homology”) of an aminoacid sequence is used to indicate the degree of consistency of aminoacid residues between the sequences to be compared. In order tocalculate identity of a given amino acid sequence to an amino acidsequence to be compared, the presence of gaps and the property of theamino acids are considered (Wilbur, Natl. Acad. Sci. U.S.A. 80:726-730(1983)). For the calculation of identity, a commercially availablesoftware BLAST (Altschul: J. Mol. Biol. 215:403-410 (1990)), FASTA(Peasron: Methods in Enzymology 183:63-69 (1990)) or the like can beused.

The “identity” value may be any value as long as it is obtained by usinga homology search program known to those skilled in the art. Forexample, for such calculation, the default (initial setting) parameterscan be used in homology algorithm BLAST (Basic local alignment searchtool) http://www.ncbi.nlm.nih.gov/BLAST/ of the National Center forBiotechnology Information (NCBI).

According to the present invention, FGFR2 comprises mutant FGFR2described below.

(2) Cell Overexpressing FGFR2

According to the present invention, a cell overexpressing FGFR2comprises, for example, a cell expressing FGFR2 for a significant amountas compared to a normal cell. In addition, according to the presentinvention, a cell overexpressing FGFR2 comprises, for example, a cellexpressing FGFR2 for at least 1.5 times higher, preferably at least 2times higher, more preferably at least 3 times higher, still morepreferably at least 4 times higher than a normal cell. Herein, accordingto the invention, a “normal cell” refers to, for example, cells otherthan cancer (e.g., undifferentiated gastric cancer) cells.

According to the present invention, a cell overexpressing FGFR2 ispreferably undifferentiated gastric cancer cell, more preferably atleast one cell selected from the group consisting of poorlydifferentiated adenocarcinoma, signet-ring cell carcinoma, mucinouscarcinoma and scirrhous gastric cancer.

An expression level of FGFR2 may be analyzed, for example, by measuringthe protein and/or the mRNA of FGFR2 expressed in the cell.

Protein can be measured, for example, by an immunochemical method (e.g.,immunohistochemistry method, immunoprecipitation, western blotting, flowcytometry, ELISA, RIA, etc.), mass spectrometry or the like, preferablyan immunochemical method, particularly preferably flow cytometry. Thesemethods may be carried out according to conventional techniques.

On the other hand, mRNA can be measured, for example, by a method suchas in situ hybridization, northern blot analysis, DNA microarray,RT-PCR, quantitative RT-PCR or the like, preferably RT-PCR orquantitative RT-PCR. These methods may be carried out according toconventional techniques.

(3) Cell Overexpressing Mutant FGFR2

According to the present invention, mutant FGFR2 comprises polypeptidescomprising an amino acid sequence having one or a few amino acidsdeleted, substituted or added, or mutated by a combination thereof in awild-type FGFR2 amino acid sequence such as the amino acid sequence(amino acids 22-822) represented by SEQ ID NO:2. Preferably, the mutantFGFR2 comprises polypeptides comprising an amino acid sequence havingone or a few amino acids deleted, substituted or added, or mutated by acombination thereof in a wild-type FGFR2 amino acid sequence such as theamino acid sequence (amino acids 22-822) represented by SEQ ID NO:2, andhaving substantially the same activity as FGFR2. According to thepresent invention, a cell expressing mutant FGFR2 comprises cellsexpressing the above-mentioned polypeptides.

Examples of mutant FGFR2 include polypeptides comprising an amino acidsequence where serine at position 267 of the amino acid sequence (aminoacids 22-822) represented by SEQ ID NO:2 is substituted by other aminoacid, preferably proline (Cancer Research. 61, 3541-3543, 2001).

In addition, examples of mutant FGFR2 include polypeptides comprising amutation site where a few amino acids at C-terminal are deleted in anamino acid sequence of wild-type FGFR2 such as amino acids 22-822 of theamino acid sequence represented by SEQ ID NO:2. Examples of mutant FGFR2include polypeptides comprising an amino acid sequence where amino acidsdownstream from at least position 813, preferably at least position 784,more preferably at least position 780, and still more preferably atleast position 769 are deleted from the amino acid sequence (amino acids22-822) represented by SEQ ID NO:2.

Preferably, mutant FGFR2 is activating mutant FGFR2. Activating mutantFGFR2 refers to mutant FGFR2 that causes autophosphorylation in aligand-independent manner and that activates intracellular signals.

The presence or the absence of FGFR2 mutation can be determined byanalyzing the gene sequence of FGFR2 or the sequence of the transcript,i.e., mRNA, of FGFR2. An example of the method for analyzing a sequenceincludes dideoxynucleotide chain termination technique (Sanger et al.,(1977) Proc. Natl. Acad. Sci. USA 74:5463). A sequence can also beanalyzed by employing an appropriate DNA sequencer.

Furthermore, the presence or the absence of FGFR2 mutation can beanalyzed, for example, by in situ hybridization, northern blot analysis,DNA microarray, RT-PCR, SSCP-PCR (Single-Strand ConformationPolymorphism-PCR) or the like. These methods may be carried outaccording to conventional techniques.

The presence or the absence of FGFR2 mutation can be analyzed, forexample, by an immunochemical method (e.g., an immunohistochemistrymethod, immunoprecipitation, western blotting, flow cytometry, ELISA,RIA, etc.). These methods may be carried out according to conventionaltechniques.

According to the present invention, a cell expressing mutant FGFR2 ispreferably an undifferentiated gastric cancer cell, more preferably atleast one cell selected from the group consisting of poorlydifferentiated adenocarcinoma, signet-ring cell carcinoma, mucinouscarcinoma and a scirrhous gastric cancer.

(4) FGFR2 Inhibitor of the Invention

Herein, a “halogen atom” refers to a fluorine atom, a chlorine atom, abromine atom or an iodine atom.

Preferable examples of a “halogen atom” include a fluorine atom and achlorine atom.

Herein, a “C₁₋₆ alkyl group” refers to a linear or branched alkyl groupwith a carbon number of 1-6, specific examples including a methyl group,an ethyl group, a 1-propyl group (n-propyl group), a 2-propyl group(i-propyl group), a 2-methyl-1-propyl group (i-butyl group), a2-methyl-2-propyl group (t-butyl group), a 1-butyl group (n-butylgroup), a 2-butyl group (s-butyl group), a 1-pentyl group, a 2-pentylgroup, a 3-pentyl group, a 2-methyl-1-butyl group, a 3-methyl-1-butylgroup, a 2-methyl-2-butyl group, a 3-methyl-2-butyl group, a2,2-dimethyl-1-propyl group, a 1-hexyl group, a 2-hexyl group, a 3-hexylgroup, a 2-methyl-1-pentyl group, a 3-methyl-1-pentyl group, a4-methyl-1-pentyl group, a 2-methyl-2-pentyl group, a 3-methyl-2-pentylgroup, a 4-methyl-2-pentyl group, a 2-methyl-3-pentyl group, a3-methyl-3-pentyl group, a 2,3-dimethyl-1-butyl group, a3,3-dimethyl-1-butyl group, a 2,2-dimethyl-1-butyl group, a2-ethyl-1-butyl group, a 3,3-dimethyl-2-butyl group and a2,3-dimethyl-2-butyl group.

Preferable examples of a “C₁₋₆ alkyl group” include a methyl group, anethyl group, a 1-propyl group, a 2-propyl group, a 2-methyl-1-propylgroup, a 2-methyl-2-propyl group, a 1-butyl group and a 2-butyl group.

Herein, a “C₁₋₆ alkylene group” refers to a divalent group derived froma “C₁₋₆ alkyl group” defined above by removing any one hydrogen atomtherefrom, specific examples including a methylene group, a 1,2-ethylenegroup, a 1,1-ethylene group, a 1,3-propylene group, a tetramethylenegroup, a pentamethylene group and a hexamethylene group.

Herein, a “C₂₋₆ alkenyl group” refers to a linear or branched alkenylgroup having one double bond and a carbon number of 2-6, specificexamples including an ethenyl group (vinyl group), a 1-propenyl group, a2-propenyl group (allyl group), a 1-butenyl group, a 2-butenyl group, a3-butenyl group, a pentenyl group and a hexenyl group.

Herein, a “C₂₋₆ alkynyl group” refers to a linear or branched alkynylgroup having one triple bond and a carbon number of 2-6, specificexamples including an ethinyl group, a 1-propynyl group, a 2-propynylgroup, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, apentynyl group and a hexynyl group.

Herein, a “C₃₋₈ cycloalkyl group” refers to a monocyclic or bicyclicsaturated aliphatic hydrocarbon group with a carbon number of 3-8,specific examples including a cyclopropyl group, a cyclobutyl group, acyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctylgroup, a bicyclo[2.1.0]pentyl group, a bicyclo[3.1.0]hexyl group, abicyclo[2.1.1]hexyl group, a bicyclo[4.1.0]heptyl group, abicyclo[2.2.1]heptyl group (norbornyl group), a bicyclo[3.3.0]octylgroup, a bicyclo[3.2.1]octyl group and a bicyclo[2.2.2]octyl group.

Preferable examples of a “C₃₋₈ cycloalkyl group” include a cyclopropylgroup, a cyclobutyl group and a cyclopentyl group.

Herein, a “C₆₋₁₀ aryl group” refers to an aromatic hydrocarbon cyclicgroup with a carbon number of 6-10, specific examples including a phenylgroup, a 1-naphthyl group, a 2-naphthyl group, an indenyl group and anazulenyl group.

A preferable example of a “C₆₋₁₀ aryl group” includes a phenyl group.

Herein, a “heteroatom” refers to a nitrogen atom, an oxygen atom or asulfur atom.

Herein, a “5-10-membered heteroaryl group” refers to an aromatic cyclicgroup having 5-10 atoms forming the ring and 1-5 heteroatoms included inthe atoms forming the ring, specific examples including a furyl group, athienyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group,a tetrazolyl group, a thiazolyl group, a pyrazolyl group, an oxazolylgroup, an isoxazolyl group, an isothiazolyl group, a furazanyl group, athiadiazolyl group, an oxadiazolyl group, a pyridyl group, a pyrazinylgroup, a pyridazinyl group, a pyrimidinyl group, a triazinyl group, apurinyl group, a pteridinyl group, a quinolyl group, an isoquinolylgroup, a naphthridinyl group, a quinoxalinyl group, a cinnolinyl group,a quinazolinyl group, a phthalazinyl group, an imidazopyridyl group, animidazothiazolyl group, an imidazoxazolyl group, a benzothiazolyl group,a benzoxazolyl group, a benzimidazolyl group, an indolyl group, anisoindolyl group, an indazolyl group, a pyrrolopyridyl group, athienopyridyl group, a furopyridyl group, a benzothiadiazolyl group, abenzoxadiazolyl group, a pyridopyrimidinyl group, a benzofuryl group, abenzothienyl group and a thienofuryl group.

Preferable examples of a “5-10-membered heteroaryl group” include afuryl group, a thienyl group, a pyrrolyl group, an imidazolyl group, athiazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolylgroup, an isothiazolyl group, a pyridyl group and a pyrimidinyl group.

Herein, a “3-10-membered nonaromatic heterocyclic group”:

(a) has 3-10 atoms forming the ring;

(b) has 1-2 heteroatoms included in the atoms forming the ring;

(c) may include 1-2 double bonds in the ring;

(d) may include 1-3 carbonyl groups, sulfinyl groups or sulfonyl groupsin the ring; and

(e) is a nonaromatic monocyclic or bicyclic group where when a nitrogenatom is included in the atoms forming the ring, the nitrogen atom mayhave a chemical bond.

Specific examples include an aziridinyl group, an azetidinyl group, apyrrolidinyl group, a piperidinyl group, an azepanyl group, an azocanylgroup, a piperazinyl group, a diazepanyl group, a diazocanyl group, adiazabicyclo[2.2.1]heptyl group, a morpholinyl group, a thiomorpholinylgroup, a 1,1-dioxothiomorpholinyl group, an oxiranyl group, an oxetanylgroup, a tetrahydrofuryl group, a dioxolanyl group, a tetrahydropyranylgroup, a dioxanyl group, a tetrahydrothienyl group, atetrahydrothiopyranyl group, an oxazolidinyl group and a thiazolidinylgroup.

Preferable examples of a “3-10-membered nonaromatic heterocyclic group”include an aziridinyl group, an azetidinyl group, a pyrrolidinyl group,a piperidinyl group, an azepanyl group, a piperazinyl group, adiazepanyl group, a morpholinyl group, a thiomorpholinyl group, a1,1-dioxothiomorpholinyl group, a tetrahydrofuryl group and atetrahydropyranyl group.

Herein, a “C₁₋₆ alkoxy group” refers to a group in which an oxygen atomis bound to the terminal of a “C₁₋₆ alkyl group” defined above, specificexamples including a methoxy group, an ethoxy group, a 1-propoxy group(n-propoxy group), a 2-propoxy group (1-propoxy group), a2-methyl-1-propoxy group (1-butoxy group), a 2-methyl-2-propoxy group(t-butoxy group), a 1-butoxy group (n-butoxy group), a 2-butoxy group(s-butoxy group), a 1-pentyloxy group, a 2-pentyloxy group, a3-pentyloxy group, a 2-methyl-1-butoxy group, a 3-methyl-1-butoxy group,a 2-methyl-2-butoxy group, a 3-methyl-2-butoxy group, a2,2-dimethyl-1-propoxy group, a 1-hexyloxy group, a 2-hexyloxy group, a3-hexyloxy group, a 2-methyl-1-pentyloxy group, a 3-methyl-1-pentyloxygroup, a 4-methyl-1-pentyloxy group, a 2-methyl-2-pentyloxy group, a3-methyl-2-pentyloxy group, a 4-methyl-2-pentyloxy group, a2-methyl-3-pentyloxy group, a 3-methyl-3-pentyloxy group, a2,3-dimethyl-1-butoxy group, a 3,3-dimethyl-1-butoxy group, a2,2-dimethyl-1-butoxy group, a 2-ethyl-1-butoxy group, a3,3-dimethyl-2-butoxy group and a 2,3-dimethyl-2-butoxy group.

Preferable examples of a “C₁₋₆ alkoxy group” include a methoxy group, anethoxy group, a 1-propoxy group, a 2-propoxy group, a 2-methyl-1-propoxygroup, a 2-methyl-2-propoxy group, a 1-butoxy group and a 2-butoxygroup.

Herein, a “C₁₋₆ alkylthio group” refers to a group in which a sulfuratom is bound to the terminal of a “C₁₋₆ alkyl group” defined above,specific examples including a methylthio group, an ethylthio group, a1-propylthio group (n-propylthio group), a 2-propylthio group(i-propylthio group), a 2-methyl-1-propylthio group (1-butylthio group),a 2-methyl-2-propylthio group (t-butylthio group), a 1-butylthio group(n-butylthio group), a 2-butylthio group (s-butylthio group), a1-pentylthio group, a 2-pentylthio group, a 3-pentylthio group, a2-methyl-1-butylthio group, a 3-methyl-1-butylthio group, a2-methyl-2-butylthio group, a 3-methyl-2-butylthio group, a2,2-dimethyl-1-propylthio group, a 1-hexylthio group, a 2-hexylthiogroup, a 3-hexylthio group, a 2-methyl-1-pentylthio group, a3-methyl-1-pentylthio group, a 4-methyl-1-pentylthio group, a2-methyl-2-pentylthio group, a 3-methyl-2-pentylthio group, a4-methyl-2-pentylthio group, a 2-methyl-3-pentylthio group, a3-methyl-3-pentylthio group, a 2,3-dimethyl-1-butylthio group, a3,3-dimethyl-1-butylthio group, a 2,2-dimethyl-1-butylthio group, a2-ethyl-1-butylthio group, a 3,3-dimethyl-2-butylthio group and a2,3-dimethyl-2-butylthio group.

Preferable examples of a “C₁₋₆ alkylthio group” include a methylthiogroup, an ethylthio group, a 1-propylthio group (n-propylthio group), a2-propylthio group (1-propylthio group), a 2-methyl-1-propylthio group(1-butylthio group), a 2-methyl-2-propylthio group (t-butylthio group),a 1-butylthio group (n-butylthio group) and a 2-butylthio group(s-butylthio group).

Herein, a “C₃₋₈ cycloalkoxy group” refers to a group in which an oxygenatom is bound to the terminal of a “C₃₋₈ cycloalkyl group” definedabove, specific examples including a cyclopropoxy group, a cyclobutoxygroup, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxygroup, a cyclooctyloxy group, a bicyclo[2.1.0]pentyloxy group, abicyclo[3.1.0]hexyloxy group, a bicyclo[2.1.1]hexyloxy group, abicyclo[4.1.0]heptyloxy group, a bicyclo[2.2.1]heptyloxy group(norbornyloxy group), a bicyclo[3.3.0]octyloxy group, abicyclo[3.2.1]octyloxy group and a bicyclo[2.2.2]octyloxy group.

Preferable examples of a “C₃₋₈ cycloalkoxy group” include a cyclopropoxygroup, a cyclobutoxy group and a cyclopentyloxy group.

Herein, a “mono-C₁₋₆ alkylamino group” refers to a group in which ahydrogen atom in an amino group is substituted with a “C₁₋₆ alkyl group”defined above, specific examples including a methylamino group, anethylamino group, a 1-propylamino group (n-propylamino group), a2-propylamino group (i-propylamino group), a 2-methyl-1-propylaminogroup (1-butylamino group), a 2-methyl-2-propylamino group (t-butylaminogroup), a 1-butylamino group (n-butylamino group), a 2-butylamino group(s-butylamino group), a 1-pentylamino group, a 2-pentylamino group, a3-pentylamino group, a 2-methyl-1-butylamino group, a3-methyl-1-butylamino group, a 2-methyl-2-butylamino group, a3-methyl-2-butylamino group, a 2,2-dimethyl-1-propylamino group, a1-hexylamino group, a 2-hexylamino group, a 3-hexylamino group, a2-methyl-1-pentylamino group, a 3-methyl-1-pentylamino group, a4-methyl-1-pentylamino group, a 2-methyl-2-pentylamino group, a3-methyl-2-pentylamino group, a 4-methyl-2-pentylamino group, a2-methyl-3-pentylamino group, a 3-methyl-3-pentylamino group, a2,3-dimethyl-1-butylamino group, a 3,3-dimethyl-1-butylamino group, a2,2-dimethyl-1-butylamino group, a 2-ethyl-1-butylamino group, a3,3-dimethyl-2-butylamino group and a 2,3-dimethyl-2-butylamino group.

Herein, a “di-C₁₋₆ alkylamino group” refers to a group in which twohydrogen atoms in an amino group are substituted with an identical ordifferent “C₁₋₆ alkyl group” defined above, specific examples includinga N,N-dimethylamino group, a N,N-diethylamino group, aN,N-di-n-propylamino group, a N,N-di-1-propylamino group, aN,N-di-n-butylamino group, a N,N-di-1-butylamino group, aN,N-di-s-butylamino group, a N,N-di-t-butylamino group, aN-ethyl-N-methylamino group, a N-n-propyl-N-methylamino group, aN-i-propyl-N-methylamino group, a N-n-butyl-N-methylamino group, aN-i-butyl-N-methylamino group, a N-s-butyl-N-methylamino group and aN-t-butyl-N-methylamino group.

Herein, a “C₂₋₇ acyl group” refers to a carbonyl group bound with a“C₁₋₆ alkyl group” defined above, specific examples including an acetylgroup, a propionyl group, an isopropionyl group, a butyryl group, anisobutyryl group, a valeryl group, an isovaleryl group and a pivaloylgroup.

Herein, a “C₂₋₇ alkoxycarbonyl group” refers to a carbonyl group boundwith a “C₁₋₆ alkoxy group” defined above, specific examples including amethoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonylgroup, a 2-propyloxycarbonyl group and a 2-methyl-2-propoxycarbonylgroup.

Herein, “that may have a substituent” means “that may have one or moresubstituents in any combination at substitutable positions”, specificexamples of substituents including a halogen atom, a hydroxyl group, athiol group, a nitro group, a cyano group, a formyl group, a carboxylgroup, an amino group, a silyl group, a methanesulfonyl group, a C₁₋₆alkyl group, a C₂₋₆ alkenyl group, a C₂₋₆ alkynyl group, a C₃₋₈cycloalkyl group, a C₆₋₁₀ aryl group, a 5-10-membered heteroaryl group,a 3-10-membered nonaromatic heterocyclic group, a C₁₋₆ alkoxy group, aC₁₋₆ alkylthio group, a C₃₋₈ cycloalkoxy group, a mono-C₁₋₆ alkylaminogroup, a di-C₁₋₆ alkylamino group, a C₂₋₇ acyl group and a C₂₋₇alkoxycarbonyl group. In this case, the C₁₋₆ alkyl group, the C₂₋₆alkenyl group, the C₂₋₆ alkynyl group, the C₃₋₈ cycloalkyl group, theC₆₋₁₀ aryl group, the 5-10-membered heteroaryl group, the 3-10-memberednonaromatic heterocyclic group, the C₁₋₆ alkoxy group, the C₁₋₆alkylthio group, the C₃₋₈ cycloalkoxy group, the mono-C₁₋₆ alkylaminogroup, the di-C₁₋₆ alkylamino group, the C₂₋₇ acyl group and the C₂₋₇alkoxycarbonyl group may each independently have 1-3 groups selectedfrom the group consisting of the following substituent groups.

<Substituent Groups>

A halogen atom, a hydroxyl group, a thiol group, a nitro group, a cyanogroup, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group, a C₂₋₆ alkenylgroup, a C₂₋₆ alkynyl group, a C₆₋₁₀ aryl group, a 5-10-memberedheteroaryl group, a 3-10-membered nonaromatic heterocyclic group, a C₁₋₆alkoxy group and a C₁₋₆ alkylthio group.

According to the present invention, an example of a FGFR2 inhibitorincludes a compound represented by General formula (I).

Hereinafter, a compound represented by General Formula (I) may also bereferred to as a “FGFR2 inhibitor I”.

(i) R¹

R¹ represents a group represented by Formula —V¹—V²—V³ (wherein, V¹represents an optionally substituted C₁₋₆ alkylene group; V² representsa single bond, an oxygen atom, a sulfur atom, a carbonyl group, asulfinyl group, a sulfonyl group, a group represented by Formula—CONR⁶—, a group represented by Formula —SO₂NR⁶—, a group represented byFormula —NR⁶SO₂—, a group represented by Formula —NR⁶CO— or a grouprepresented by Formula —NR⁶— (wherein, R⁶ represents a hydrogen atom, anoptionally substituted C₁₋₆ alkyl group or an optionally substitutedC₃₋₈ cycloalkyl group); V³ represents a hydrogen atom, an optionallysubstituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenylgroup, an optionally substituted C₂₋₆ alkynyl group, an optionallysubstituted C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ arylgroup, an optionally substituted 5-10-membered heteroaryl group or anoptionally substituted 3-10-membered nonaromatic heterocyclic group).

A preferable example of R¹ includes a C₁₋₆ alkyl group provided that R¹may have a substituent selected from a 3-10-membered nonaromaticheterocyclic group, a hydroxyl group, a C₁₋₆ alkoxy group, an aminogroup, a mono-C₁₋₆ alkylamino group and a di-C₁₋₆ alkylamino group whichmay have a C₁₋₆ alkyl group.

More preferable examples of R¹ include a methyl group and a grouprepresented by any one of the following formulae

(wherein, R^(a3) represents a methyl group; R^(a1) represents a hydrogenatom or a hydroxyl group; R^(a2) represents a methoxy group, an ethoxygroup, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinylgroup, a dimethylamino group or a diethylamino group).

Still more preferable examples of R¹ include a methyl group and a2-methoxyethyl group.

(ii) R²

R² represents a cyano group, an optionally substituted C₁₋₆ alkoxygroup, a carboxyl group, an optionally substituted C₂₋₇ alkoxycarbonylgroup or a group represented by Formula —CONV^(a11)V^(a12) (wherein,V^(a11) represents a hydrogen atom, an optionally substituted C₁₋₆ alkylgroup, an optionally substituted C₂₋₆ alkenyl group, an optionallysubstituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, anoptionally substituted 5-10-membered heteroaryl group or an optionallysubstituted 3-10-membered nonaromatic heterocyclic group; V^(a12)represents a hydrogen atom, an optionally substituted C₁₋₆ alkyl group,an optionally substituted C₂₋₆ alkenyl group, an optionally substitutedC₂₋₆ alkynyl group, an optionally substituted C₃₋₈ cycloalkyl group, anoptionally substituted C₆₋₁₀ aryl group, an optionally substituted5-10-membered heteroaryl group, an optionally substituted 3-10-memberednonaromatic heterocyclic group, a hydroxyl group, an optionallysubstituted C₁₋₆ alkoxy group or an optionally substituted C₃₋₈cycloalkoxy group).

Preferable examples of R² include a cyano group or a group representedby Formula —CONV^(a11)V^(a12) (wherein, V^(a11) and V^(a12) have thesame meaning as defined above).

More preferable examples of R² include a cyano group or a grouprepresented by Formula —CONHV^(a16) (wherein, V^(a16) represents ahydrogen atom, a C₁₋₆ alkyl group, a C₃₋₈ cycloalkyl group, a C₁₋₆alkoxy group or a C₃₋₈ cycloalkoxy group, provided that V^(a16) may havea substituent selected from a halogen atom, a cyano group, a hydroxylgroup and a C₁₋₆ alkoxy group).

A still more preferable example of R² includes a group represented byFormula —CONHV^(a17) (wherein, V^(a17) represents a hydrogen atom, aC₁₋₆ alkyl group or a C₁₋₆ alkoxy group).

The most preferable example of R² includes a group represented byFormula —CONHV^(a18) (wherein, V^(a18) represents a hydrogen atom, amethyl group or a methoxy group).

(iii) Y¹

Y¹ represents a group represented by the following formula

(wherein, R⁷ and R⁸ each independently represent a hydrogen atom, ahalogen atom, a cyano group, a nitro group, an amino group, anoptionally substituted C₁₋₆ alkyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₁₋₆ alkoxy group, anoptionally substituted C₁₋₆ alkylthio group, a formyl group, anoptionally substituted C₂₋₇ acyl group, an optionally substituted C₂₋₇alkoxycarbonyl group or a group represented by Formula —CONV^(d1)V^(d2)(wherein, V^(d1) and V^(d2) each independently represent a hydrogen atomor an optionally substituted C₁₋₆ alkyl group);W¹ and W² each independently represent an optionally substituted carbonatom or nitrogen atom).

A preferable example of Y¹ includes a group represented by the followingformula

(wherein, R⁷¹ represents a hydrogen atom or a halogen atom).

(iv) R³ and R⁴

R³ and R⁴ each independently represent a hydrogen atom, an optionallysubstituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenylgroup, an optionally substituted C₂₋₆ alkynyl group, an optionallysubstituted C₃₋₈ cycloalkyl group, an optionally substituted C₂₋₇ acylgroup or an optionally substituted C₂₋₇ alkoxycarbonyl group.

A preferable example of R³ and R⁴ includes a hydrogen atom.

(v) R⁵

R⁵ represents a hydrogen atom, an optionally substituted C₁₋₆ alkylgroup, an optionally substituted C₂₋₆ alkenyl group, an optionallysubstituted C₂₋₆ alkynyl group, an optionally substituted C₃₋₈cycloalkyl group, an optionally substituted C₆₋₁₀ aryl group, anoptionally substituted 5-10-membered heteroaryl group or an optionallysubstituted 3-10-membered nonaromatic heterocyclic group.

Preferable examples of R⁵ include a hydrogen atom, an optionallysubstituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenylgroup, an optionally substituted C₂₋₆ alkynyl group, an optionallysubstituted C₃₋₈ cycloalkyl group, an optionally substituted C₆₋₁₀ arylgroup and an optionally substituted 3-10-membered nonaromaticheterocyclic group.

More preferable examples of R⁵ include a hydrogen atom, a C₁₋₆ alkylgroup, a C₃₋₈ cycloalkyl group and a C₆₋₁₀ aryl group (provided that R⁵may have at least one substituent selected from the group consisting ofa halogen atom and a methanesulfonyl group).

More preferable examples of R⁵ include a methyl group, an ethyl groupand a cyclopropyl group.

Furthermore, preferable examples of the compound represented by GeneralFormula (I) include:

-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea;-   N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N′-cyclopropyl    urea;-   N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide;-   4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide;-   N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea;-   N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea;-   4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic    acid (2-cyanoethyl)amide; and-   N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropyl    urea.

More preferable examples of the compound represented by General Formula(I) include:

-   4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;-   N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;-   4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide;    and-   N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide.

A still more preferable example of the compound represented by GeneralFormula (I) includes4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(see Formula (II)).

The most preferable example of the FGFR2 inhibitor I includesmethanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

A compound represented by General formula (I) may be produced by a knownmethod such as methods described in International Publications Nos.02/32872 (WO02/32872) and 2005/063713 (WO2005/063713).

In addition, a FGFR2 inhibitor according to the present invention maynot be a compound represented by General Formula (I) above (hereinafter,also referred to as a “FGFR2 inhibitor II”) as long as it has anactivity of inhibiting the kinase activity of FGFR2. Examples of FGFR2inhibitors II include:

5-(5-fluoro-2-oxo-1,2-dihydroindole-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylicacid (2-diethylaminoethyl)amide (hereinafter, also referred to as“SU11248”; Journal of Medicinal Chemistry., 46:1116-9, 2003, WO01/060814) (see Formula (III)),

N-(3-trifluoromethyl-4-chlorophenyl)-N′-(4-(2-methylcarbamoylpyridine-4-yl)oxyphenyl)urea(hereinafter, also referred to as “BAY 43-9006” or “sorafenib”;WO00/42012) (see Formula (IV)),

6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridine-2-yl)ethenyl]indazole(hereinafter, also referred to as “AG013736”; WO0/002369) (see Formula(V)), and

N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea(hereinafter, also referred to as “KRN951”; WO02/088110) (see Formula(VI))

SU11248, BAY 43-9006, AG013736 and KRN951 may be produced by a knownmethod such as methods described in respective publications mentionedabove.

According to the present invention, a FGFR2 inhibitor may form apharmacologically acceptable salt with acid or base. The FGFR2 inhibitorof the invention also comprises such pharmacologically acceptable salts.Examples of salts formed with acids include inorganic acid salts such ashydrochloride salts, i salts, sulfate salts and phosphate salts, andorganic acid salts such as formic acid, acetic acid, lactic acid,succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid,stearic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid,p-toluenesulfonic acid and trifluoroacetic acid. Examples of saltsformed with bases include alkali metal salts such as sodium salt andpotassium salt, alkaline earth metal salts such as calcium salt andmagnesium salt, organic base salts such as trimethylamine,triethylamine, pyridine, picoline, dicyclohexylamine, N,N′-dibenzylethylenediamine, arginine and lysine and ammonium salts.

Furthermore, according to the present invention, the FGFR2 inhibitor mayexist as a solvate or an optical isomer. According to the presentinvention, the FGFR2 inhibitor comprises such solvates and opticalisomers. Examples of solvates include hydrates and nonhydrates,preferably hydrates. Examples of solvents include water, alcohols (forexample, methanol, ethanol and n-propanol) and dimethylformamide.

Moreover, according to the present invention, the FGFR2 inhibitor may becrystalline or amorphous. If a crystalline polymorph exists, it mayexist as one type of any crystalline or mixture thereof.

According to the present invention, the FGFR2 inhibitor also comprisestheir metabolites generated by undergoing metabolism such as oxidation,reduction, hydrolysis and conjugation in vivo. According to the presentinvention, the FGFR2 inhibitor also comprises compounds that generatethe FGFR2 inhibitor by undergoing metabolism such as oxidation,reduction and hydrolysis in vivo.

Preferably, the FGFR2 inhibitor of the invention is a substance that hasan activity of inhibiting the FGFR2 kinase activity (hereinafter, alsoreferred to as an “FGFR2 inhibitory activity”). Herein, an “FGFR2 kinaseactivity” refers to an activity of FGFR2 to phosphorylate a tyrosineresidue of own protein or other protein.

Examples of methods for determining a FGFR2 inhibitory activity of theFGFR2 inhibitor include cell free kinase assay, western blotting, cellgrowth assay and viability assay. Examples of the cell growth assayinclude tritium thymidine uptake method, MTT method, XTT method (cellcounting kit-8 (Dojindo Laboratories)), AlamarBlue technique, NeutralRed technique, BrdU technique, Ki67 staining and PCNA staining. Examplesof the viability assay include TUNNEL staining, Caspase-3 cleavagedetection and PARP cleavage detection. These methods may be carried outaccording to conventional techniques (Blood. 2005, 105, 2941-2948.,Molecular Cancer Therapeutics. 2005, 4, 787-798).

Hereinafter, an exemplary method for determining a FGFR2 inhibitoryactivity will be described.

The FGFR2 inhibitory activity can be determined by cell free kinaseassay.

FGFR2 can be prepared by a gene-engineering technique according to aconventional method. For example, according to the method of BaculovirusExpression System, human recombinant GST fusion protein, humanrecombinant histidine-tag fusion protein or the like may be expressed inan insect cell (Spondoptea frugiperda 9 (Sf9)). Furthermore, theexpressed recombinant protein can be purified by affinity chromatography(e.g., GSH-agarose (Sigma) or Ni-NTH-agarose (Qiagen)). The purity andidentification of the protein can be confirmed by SDS-PAGE, silverstaining and western blotting using an antibody specific to FGFR2.

The cell free kinase assay may be carried out as follows.

First, to each well of a plate (e.g., 96-well, 384-well, etc.), 25 μl ofa solution containing an ATP solution, a test substance, 5-10 mU ofFGFR2 recombinant protein and 0.1 mg/ml Poly(Glu, Tyr)_(4:1) may beadded. To this mixture, MgATP is added to initiate reaction.

25 μl of this mixture may contain 8 mM MOPS (pH 7.0), 0.2 mM EDTA, 2.5mM MnCl₂, 10 mM Mg acetate and the like. ATP used in this case may belabeled with a radioisotope such as [γ-³²P]-ATP and [γ-³³P]-ATP.

The reaction may be terminated by adding 5 μL of 3% phosphoric acidfollowing incubation for a given period of time.

Each well may be subjected to an appropriate washing procedure.

A FGFR2 inhibitory activity can be assessed by determining the amount ofATP incorporation. When a radioactive isotope-labeled ATP mentionedabove is used, the amount of ATP incorporation can be assessed bydetermination of the radioactivity captured on the plate with ascintillation counter. Alternatively, a certain amount of the reactionsolution may be spotted onto a filter to measure the radioactivitythereof with a scintillation counter. The filter may be subjected to anappropriate washing procedure.

The FGFR2 inhibitory activity of the compound can be assessed by thismethod.

2. Therapeutic Substance for Gastric Cancer

According to the present invention, a therapeutic substance for gastriccancer is not particularly limited as long as it is a substance used fortreating gastric cancer, a substance whose therapeutic use is suitablefor gastric cancer or a substance having anti-tumor action againstgastric cancer. In addition, the therapeutic substance for gastriccancer of the invention may be a therapeutic drug for gastric cancerobtained by formulating the compound as an active ingredient.

According to the present invention, examples of therapeutic substancesfor gastric cancer include carboquone, nimustine, 5-fluorouracil analogs(e.g., 5-fluorouracil, tegafur, UFT, doxifluridine and carmofur, S-1),doxorubicin (adriamycin), mitomycin C, aclarubicin, pirarubicin,epirubicin, irinotecan, paclitaxel analogs (e.g., docetaxel andpaclitaxel), cis-platinum (Cisplatin)), preferably 5-fluorouracil, S-1,irinotecan, docetaxel, paclitaxel or cis-platinum, more preferably,irinotecan, 5-fluorouracil or paclitaxel. Therapeutic substances forgastric cancer may be produced according to a known method or they maybe purchased.

Carboquone is available by purchasing Esquinon (Registered Trademark)(Sankyo).

Nimustine or nimustine hydrochloride is available by purchasing Nidran(Registered Trademark) (Sankyo).

5-Fluorouracil is available by purchasing 5-FU (Kyowa Hakko).

Tegafur is available by purchasing Futraful (Registered Trademark)(Taiho Pharmaceutical Co., Ltd.).

UFT refers to a combinational agent of tegafur and uracil. UFT isavailable by purchasing UFT (Registered Trademark) (Taiho PharmaceuticalCo., Ltd.).

Doxifluridine is available by purchasing Furtulon (Registered Trademark)(Chugai Pharmaceutical Co., Ltd.).

Carmofur is available by purchasing Mifurol (Registered Trademark)(Schering).

S-1 refers to a combinational agent of tegafur, gemeracil and oteracilpotassium. S-1 is available by purchasing TS-1 (Registered Trademark)(Taiho Pharmaceutical Co., Ltd.).

Doxorubicin (adriamycin) or doxorubicin hydrochloride is available bypurchasing Adriacin (Registered Trademark) (Kyowa Hakko).

Mitomycin C is available by purchasing mitomycin (Kyowa Hakko).

Aclarubicin or aclarubicin hydrochloride is available by purchasingAclacinon (Registered Trademark) (Astellas Inc.).

Pirarubicin or pirarubicin hydrochloride is available by purchasingPinorubin (Registered Trademark) (Nippon Kayaku Co., Ltd.) orTherarubicin (Registered Trademark) (Meiji Seika Kaisya, Ltd.).

Epirubicin or epirubicin hydrochloride is available by purchasingFarmorubicin (Registered Trademark) (Kyowa Hakko) or Epirubicin(Registered Trademark) (Nippon Kayaku Co., Ltd.).

Irinotecan or irinotecan hydrochloride is available by purchasing Campto(Registered Trademark) (Yakult). It is also available by purchasingTopotecin (Registered Trademark) (Daiichi Seiyaku).

Docetaxel or docetaxel hydrate is available by purchasing Taxoere(Registered Trademark) (Sanofi-aventis).

Paclitaxel is available by purchasing Taxol (Registered Trademark)(Bristol-Myers Squibb Company) or by purchasing Paclitaxel (NipponKayaku Co., Ltd.) or Paclitaxel (Calbiochem).

Cis-platinum (Cisplatin) is available by purchasing Randa (RegisteredTrademark) (Nippon Kayaku Co., Ltd.) or Briplatin (Registered Trademark)(Bristol-Myers Squibb Company).

Since a FGFR2 inhibitor of the present invention has an anti-tumoraction against undifferentiated gastric cancer, it is also comprised inthe therapeutic substances for gastric cancer. In this case, thetherapeutic substance for gastric cancer is preferably a FGFR2 inhibitorI or II, and more preferably a FGFR inhibitor II.

According to the present invention, the therapeutic substance forgastric cancer may form a pharmacologically acceptable salt with acid orbase. The therapeutic substance for gastric cancer according to theinvention also comprises such pharmacologically acceptable salts.Examples of salts formed with acids include inorganic acid salts such ashydrochloride salts, hydrobromate salts, sulfate salts and phosphatesalts, and organic acid salts such as formic acid, acetic acid, lacticacid, succinic acid, fumaric acid, maleic acid, citric acid, tartaricacid, stearic acid, benzoic acid, methanesulfonic acid, benzenesulfonicacid, p-toluenesulfonic acid and trifluoroacetic acid. Examples of saltsformed with bases include alkali metal salts such as sodium salt andpotassium salt, alkaline earth metal salts such as calcium salt andmagnesium salt, organic base salts such as trimethylamine,triethylamine, pyridine, picoline, dicyclohexylamine, N,N′-dibenzylethylenediamine, arginine and lysine, and ammonium salts.

Furthermore, according to the present invention, the therapeuticsubstance for gastric cancer may exist as a solvate or an opticalisomer. According to the present invention, the therapeutic substancefor gastric cancer comprises such solvates and optical isomers. Examplesof solvates include hydrates and nonhydrates, preferably hydrates.Examples of solvents include water, alcohols (for example, methanol,ethanol and n-propanol) and dimethylformamide.

Moreover, according to the present invention, the therapeutic substancefor gastric cancer may be crystalline or amorphous. If a crystallinepolymorph exists, it may exist as one type of any crystalline forms ormixture thereof.

According to the present invention, the therapeutic substance forgastric cancer also comprises their metabolites generated by undergoingmetabolism such as oxidation, reduction, hydrolysis and conjugation invivo. According to the present invention, the therapeutic substance forgastric cancer also comprises compounds that generate the therapeuticsubstance for gastric cancer by undergoing metabolism such as oxidation,reduction and hydrolysis in vivo.

3. Pharmaceutical Composition, Therapeutic Agent, Kit and TherapeuticMethod

The present invention is characterized in that a FGFR2 inhibitor iscombined with a therapeutic substance for gastric cancer. Specifically,the present invention relates to a therapeutic agent, a kit and atherapeutic method for undifferentiated gastric cancer characterized inthat the followings are combined: (i) a FGFR2 inhibitor I and atherapeutic substance for gastric cancer; (ii) a FGFR2 inhibitor I and aFGFR2 inhibitor II; or (iii) a FGFR2 inhibitor II and a therapeuticsubstance for gastric cancer. Preferably, the therapeutic agent of theinvention is used for a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2.

Herein, undifferentiated gastric cancer comprises poorly differentiatedadenocarcinoma, signet-ring cell carcinoma and mucinous carcinoma(Japanese Classification of Gastric Carcinoma “Igan-Toriatsukai Kiyaku”(13th ed.)). In the case of undifferentiated gastric cancer, cancercells are likely to diffuse and likely to develop fibrosis that leads toscirrhous gastric cancer. Thus, the therapeutic agent of the inventionis effective against at least one gastric cancer selected from the groupconsisting of poorly differentiated adenocarcinoma, signet-ring cellcarcinoma, mucinous carcinoma and scirrhous gastric cancer.

The therapeutic agent of the invention may be administered to a mammal(e.g., human, rat, rabbit, sheep, pig, bovine, cat, dog, monkey, etc.).

The pharmaceutical composition of the invention comprises a FGFR2inhibitor and a therapeutic substance for gastric cancer, specifically,(i) a FGFR2 inhibitor I and a therapeutic substance for gastric cancer;(ii) a FGFR2 inhibitor I and a FGFR2 inhibitor II; or (iii) a FGFR2inhibitor II and a therapeutic substance for gastric cancer, which isadministered to a living organism comprising at least one selected fromthe group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2.

The pharmaceutical composition of the invention may be used as atherapeutic agent for a disease characterized by comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2. An example of such a disease includesundifferentiated gastric cancer.

The pharmaceutical composition of the invention may be administered to aliving organism, i.e., a mammal (e.g., human, rat, rabbit, sheep, pig,bovine, cat, dog, monkey, etc.). These living organisms of the presentinvention may comprise either a cell overexpressing FGFR2 or a cellexpressing mutant FGFR2, or both of them.

According to the present invention, treatment comprises relievingsymptoms of the disease, retarding progression of the disease,eliminating symptoms of the disease, improving prognosis of the diseaseand preventing recurrence of the disease.

According to the present invention, a therapeutic agent for cancer alsocomprises anti-tumor agents, agents for suppressing cancer metastasis,agents for improving cancer prognosis, agents for preventing of cancerrecurrence and the like.

The effect of treatment may be confirmed by observation of an x-raypicture, CT or the like, by histopathological diagnosis by biopsy oraccording to tumor marker values.

According to the present invention, a FGFR2 inhibitor is as described in“1. FGFR2 inhibitor”. The FGFR2 inhibitor of the invention is, forexample, a FGFR2 inhibitor I such as a compound represented by GeneralFormula (I), more preferably,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,and more preferably methanesulfonate of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.

On the other hand, the FGFR2 inhibitor of the invention is a FGFR2inhibitor II, a substance that shows FGFR2 inhibitory activity and isnot comprised in compounds represented by General Formula (I), which ispreferably SU11248, BAY43-9006, AG013736 or KRN951.

According to the present invention, a therapeutic substance for gastriccancer is as described in “2. Therapeutic substance for gastric cancer”,and it is preferably irinotecan, 5 or paclitaxel. Since a FGFR2inhibitor has an anti-tumor activity against undifferentiated gastriccancer, it may be included in a therapeutic substance for gastriccancer.

Preferable embodiments of combinations of FGFR2 inhibitors andtherapeutic substances for gastric cancer according to the presentinvention are described below.

(1) According to the present invention, when a FGFR2 inhibitor is acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof (a FGFR2 inhibitor I), itis preferably used in combination with a therapeutic substance forgastric cancer described in “2. Therapeutic substance for gastriccancer” above.

(2) According to the present invention, when a FGFR2 inhibitor is acompound represented by General Formula (I), a pharmacologicallyacceptable salt thereof or a solvate thereof (a FGFR2 inhibitor I), itis preferably used in combination with a FGFR2 inhibitor that is notcomprised in compounds represented by General Formula (I) (FGFR2inhibitors II) such as SU11248, BAY43-9006, AG03736, KRN951 or the like.

(3) According to the present invention, when a FGFR2 inhibitor is aFGFR2 inhibitor that is not comprised in compounds represented byGeneral Formula (I) (FGFR2 inhibitors II), it is preferably used incombination with a therapeutic substance for gastric cancer described in“2. Therapeutic substance for gastric cancer” above.

According to the present invention, the phrase “in combination” refersto a combination of compounds for combination use, and includes bothmodes where separate substances are used in combination uponadministration or where they are provided as a mixture.

The therapeutic agent of the invention is also provided in a form of atherapeutic agent for undifferentiated gastric cancer comprising a FGFR2inhibitor I for administration to a patient in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II.Furthermore, the therapeutic agent of the invention is also provided ina form of a therapeutic agent for treating undifferentiated gastriccancer comprising a FGFR2 inhibitor II or in a form of a therapeuticagent for treating gastric cancer comprising a therapeutic substance forgastric cancer, for administration to a patient in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II.

Moreover, a pharmaceutical composition of the invention is also providedin a form of a pharmaceutical composition comprising a FGFR2 inhibitor Ifor administration to a patient in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor II, for administrationto a living organism comprising at least one selected from the groupconsisting of a cell overexpressing FGFR2 and a cell expressing mutantFGFR2. The pharmaceutical composition of the invention is also providedin a form of a pharmaceutical composition comprising a FGFR2 inhibitorII or a therapeutic substance for gastric cancer for administration to apatient in combination with a therapeutic substance for gastric canceror a FGFR2 inhibitor II, for administration to the above-mentionedliving organism.

A FGFR2 inhibitor I and a therapeutic substance for gastric cancer or aFGFR2 inhibitor II, or a FGFR2 inhibitor II and a therapeutic substancefor gastric cancer may be administered simultaneously or separately. Theterm “simultaneously” means that they are administered at the sametiming in a single administration schedule and does not necessarily meanthat they are administered at exactly the same moment. The term“separately” means that they are administered at different timings in asingle administration schedule.

The kit of the present invention is characterized by comprising a set ofa formulation comprising a FGFR2 inhibitor I and a formulationcomprising a therapeutic substance for gastric cancer or a FGFR2inhibitor II. In addition, the kit of the present invention ischaracterized by comprising a set of a formulation comprising a FGFR2inhibitor II and a formulation comprising a therapeutic substance forgastric cancer. The form of the formulations comprised in the kit of theinvention is not particularly limited as long as they contain thesubstances mentioned above. The kit of the invention is useful as a kitfor treating undifferentiated gastric cancer.

The formulations in the kit of the invention may be mixed together, orthey may be kept separately and packed together. These formulations maybe administered simultaneously or one after the other.

The therapeutic agent, the pharmaceutical composition, the kit or themethod for treating undifferentiated gastric cancer of the invention mayfurther include one or more other anti-tumor agents in combination. Suchanti-tumor agents are not particularly limited as long as they have ananticancer activity.

The therapeutic agent, the pharmaceutical composition or the kit of theinvention may be administered either orally or parenterally.

Upon use of the therapeutic agent, the pharmaceutical composition or thekit of the invention, the given dose of the FGFR2 inhibitor differsdepending on the degree of the symptom, age, sex, weight and sensitivitydifference of the patient, administration mode, administration period,administration interval, nature, prescription and type of thepharmaceutical formation and the type of the active ingredient. Usually,but without limitation, the dose is 0.1-1000 mg/day, preferably 0.5-100mg/day and more preferably 1-30 mg/day for an adult (weight 60 kg),which may be usually administered once to three times a day.

Upon use of the therapeutic agent, the pharmaceutical composition or thekit of the invention, the given dose of the therapeutic substance forgastric cancer is usually, but without limitation, 0.1-6000 mg/day,preferably 10-4000 mg/day and more preferably 50-2000 mg/day for anadult (weight 60 kg), which may be usually administered once to threetimes a day.

The amount of the FGFR2 inhibitor I used is not particularly limited,and differs depending on the individual combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor II. For example, theamount of the FGFR2 inhibitor I is about 0.01-100 times (weight ratio),more preferably about 0.1-10 times (weight ratio) the amount of thetherapeutic substance for gastric cancer or the FGFR2 inhibitor II.

Similarly, the amount of the FGFR2 inhibitor II used is not particularlylimited, and differs depending on the combination with a therapeuticsubstance for gastric cancer. For example, the amount of the FGFR2inhibitor II is about 0.01-100 times (weight ratio), more preferablyabout 0.1-10 times (weight ratio) the amount of the therapeuticsubstance for gastric cancer.

Although the pharmaceutical composition or the therapeutic agent of theinvention may be used directly, they are generally made intoformulations while mixing with appropriate additives.

A FGFR2 inhibitor or a therapeutic substance for gastric cancercontained in the kit of the invention may be made into a formulationwhile mixing with appropriate additives.

Examples of such additives include excipients, binders, lubricants,disintegrants, colorants, flavoring agents, emulsifiers, surfactants,solubilizing agents, suspending agents, tonicity agents, buffers,antiseptic agents, antioxidant agents, stabilizers, absorption promotersand the like that are generally used for medicine. If required, they maybe used in combination. Examples of such additive are mentioned below.

Excipients: lactose, sucrose, glucose, cornstarch, mannitol, sorbitol,starch, alpha-starch, dextrin, crystalline cellulose, light anhydroussilicic acid, aluminum silicate, calcium silicate, magnesiumaluminometasilicate and calcium hydrogen phosphate.

Binders: for example, polyvinyl alcohol, methyl cellulose, ethylcellulose, gum arabic, tragacanth, gelatin, shellack, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose sodium,polyvinylpyrrolidone and macrogol.

Lubricants: magnesium stearate, calcium stearate, sodium stearylfumarate, talc, polyethyleneglycol and colloid silica.

Disintegrants: crystalline cellulose, agar, gelatin, calcium carbonate,sodium hydrogen carbonate, calcium citrate, dextrin, pectin, lowsubstituted hydroxypropylcellulose, carboxymethylcellulose,carboxymethylcellulose calcium, croscarmellose sodium, carboxymethylstarch and carboxymethyl starch sodium.

Colorants: ferric oxide, yellow ferric oxide, carmine, caramel,beta-carotene, titanium oxide, talc, riboflavin sodium phosphate, yellowaluminum lake and the like that are approved as additives in drugs.

Flavoring agents: cocoa powder, menthol, aromatic acid, peppermint oil,camphor and cinnamon powder.

Emulsifiers and surfactants: stearyltriethanolamine, sodium laurylsulfate, laurylaminopropionate, lecithin, glycerine monostearate,sucrose fatty acid ester and glycerine fatty acid ester.

Solubilizing agents: polyethyleneglycol, propylene glycol, benzylbenzoate, ethanol, cholesterol, triethanolamine, sodium carbonate,sodium citrate, Polysorbate 80 and nicotine acid amide.

Suspending agents: for example, in addition to the surfactants mentionedabove, hydrophilic polymers such as polyvinyl alcohol,polyvinylpyrrolidone, methylcellulose, hydroxymethylcellulose,hydroxyethylcellulose, hydroxypropylcellulose and the like.

Tonicity agents: glucose, sodium chloride, mannitol and sorbitol.

Buffers: buffers such as phosphate, acetate, carbonate, citrate and thelike.

Antiseptic agents: methylparaben, propylparaben, chlorobutanol, benzylalcohol, phenethyl alcohol, dehydroacetic acid and sorbic acid.

Antioxidant agents: hydrosulfate, ascorbic acid and alpha-tocopherol.

Stabilizers: those generally used for medicine.

Absorption promoters: those generally used for medicine.

If required, components such as vitamins and amino acids may be blended.

Examples of the above-mentioned formulations include oral formulationssuch as tablets, powder, granule, fine granule, capsule, syrup, lozengeand inhaler; external formulations such as suppository, ointment, eyeointment, poultice strip, eye-drops, nasal drops, eardrops, skin patchand lotion; and injectable formulations.

The oral formulations mentioned above may be formulated by appropriatelycombining the additives mentioned above. If necessary, surface of theseformulations may be coated.

The external formulations mentioned above may be formulated byappropriately combining the additives mentioned above, particularlyexcipients, binders, flavoring agents, emulsifiers, surfactants,solubilizing agents, suspending agent, tonicity agents, antisepticagents, antioxidant agents, stabilizers and absorption promoters.

The injectable formulations mentioned above may be formulated byappropriately combining the additives mentioned above, particularlyemulsifiers, surfactants, solubilizing agents, suspending agents,tonicity agents, buffers, antiseptic agents, antioxidant agents,stabilizers and absorption promoters. The injectable formulations may beused through means such as infusion, intramuscular injection,subcutaneous injection, intradermal injection and intravenous injection.

The therapeutic agent, the pharmaceutical composition or the kit of theinvention can also comprise a packaging container, an instruction, apackage insert or the like in addition to the FGFR2 inhibitor and/or thetherapeutic substance for gastric cancer mentioned above. The packagingcontainer, the instruction, the package insert or the like may beprinted with description of a combination for using the compounds incombination, and description of usage and dose for using separatesubstances in combination upon administration or for use of them as amixture. The usage and dose may be described by referring to thedescription above.

The kit of the invention may comprise: (a) at least one selected fromthe group consisting of a packaging container, an instruction and apackage insert describing combination use of a FGFR2 inhibitor I with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II; and(b) a therapeutic agent for undifferentiated gastric cancer comprisingthe FGFR2 inhibitor I. Moreover, the kit of the invention may comprise:(a)′ at least one selected from the group consisting of a packagingcontainer, an instruction and a package insert describing combinationuse of a FGFR2 inhibitor II with a therapeutic substance for gastriccancer; and (b)′ a therapeutic agent for undifferentiated gastric cancercomprising the FGFR2 inhibitor II or a therapeutic agent for treatinggastric cancer comprising the therapeutic substance for gastric cancer.

The kit of the invention may comprise: (a) above; and (b)″ apharmaceutical composition comprising a FGFR2 inhibitor I foradministration to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2. In addition, the kit of the invention maycomprise: (a)′ above; and (b)′″ a pharmaceutical composition comprisinga FGFR2 inhibitor II or a therapeutic substance for gastric cancer foradministration to the above-mentioned living organism.

These kits are useful for treating undifferentiated gastric cancer. Thepackaging container, the instruction, the package insert of the like maybe printed with description for using the substances in combination, anddescription of usage and dose for using separate substances incombination upon administration or for use of them as a mixture. Theusage and dose may be determined by referring to the descriptions of thetherapeutic agent, the pharmaceutical composition and the kit above.

The present invention also comprises a method for treatingundifferentiated gastric cancer characterized by administering effectivedosages of a FGFR2 inhibitor I and a therapeutic substance for gastriccancer or a FGFR2 inhibitor II to a patient. The present invention alsocomprises a method for treating undifferentiated gastric cancercharacterized by administering effective dosages of a FGFR2 inhibitor IIand a therapeutic substance for gastric cancer to a patient.

Furthermore, the present invention comprises a method for treating adisease characterized by administering effective dosages of a FGFR2inhibitor I and a therapeutic substance for gastric cancer or a FGFR2inhibitor II to a living organism comprising at least one selected fromthe group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2. The present invention also comprises a methodfor treating a disease characterized by administering effective dosagesof a FGFR2 inhibitor II and a therapeutic substance for gastric cancerto the living organism. According to the present invention, the diseaseis preferably undifferentiated gastric cancer.

According to the therapeutic method of the invention, the route and themethod for administering the FGFR2 inhibitor are not particularlylimited but reference may be made to the description of thepharmaceutical composition or the therapeutic agent of the inventionabove.

The present invention comprises use of a FGFR2 inhibitor I for producinga therapeutic agent for undifferentiated gastric cancer in combinationwith a therapeutic substance for gastric cancer or a FGFR2 inhibitor II.The present invention also comprises use of a FGFR2 inhibitor II or atherapeutic substance for gastric cancer for producing a therapeuticagent for undifferentiated gastric cancer in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II.

In addition, the present invention comprises use of a FGFR2 inhibitor Ifor producing a pharmaceutical composition in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II foradministration to a living organism comprising at least one selectedfrom the group consisting of a cell overexpressing FGFR2 and a cellexpressing mutant FGFR2. The present invention also comprises use of aFGFR2 inhibitor II or a therapeutic substance for gastric cancer forproducing a pharmaceutical composition in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor II for administrationto the above-mentioned living organism. According to the use of theinvention, the pharmaceutical composition is useful as a therapeuticagent for undifferentiated gastric cancer.

The present invention comprises a FGFR2 inhibitor I for a therapeuticagent for undifferentiated gastric cancer in combination with atherapeutic substance for gastric cancer or a FGFR2 inhibitor II. Thepresent invention also comprises a FGFR2 inhibitor II or a therapeuticsubstance for gastric cancer for a therapeutic agent forundifferentiated gastric cancer in combination with a therapeuticsubstance for gastric cancer or a FGFR2 inhibitor II.

Moreover, the present invention comprises a FGFR2 inhibitor I for apharmaceutical composition in combination with a therapeutic substancefor gastric cancer or a FGFR inhibitor II for administration to a livingorganism comprising at least one selected from the group consisting of acell overexpressing FGFR2 and a cell expressing mutant FGFR2. Thepresent invention also comprises a FGFR2 inhibitor II or a therapeuticsubstance for gastric cancer for a pharmaceutical composition incombination with a therapeutic substance for gastric cancer or a FGFR2inhibitor II for administration to the above-mentioned living organism.According to the present invention, the pharmaceutical composition isuseful as a therapeutic agent for undifferentiated gastric cancer.

Hereinafter, the present invention will be illustrated by way ofspecific examples, although the invention should not be limited thereto.

EXAMPLE 1 Combination Use of the Compound of the Invention andIrinotecan Hydrochloride in Subcutaneous Transplanted (Xenograft) Models(In Vivo) of Human Scirrhous Gastric Cancer Cell Line (HSC-39)

Human scirrhous gastric cancer cell line HSC-39 (purchased fromImmuno-Biological Laboratories Co,. Ltd.) was cultured in RPMI1640(containing 10% FBS) in a 5% carbon dioxide gas incubator at 37° C. toabout 80% confluence, and then the cells were collected withtrypsin-EDTA. A 5×10⁷ cells/mL suspension was prepared with a phosphatebuffer, and each 0.1 mL of the resulting cell suspension wassubcutaneously transplanted to nude mice at the side of their bodies.

Twelve days after the transplantation,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(3, 10 or 30 mg/kg, once a day for four weeks, oral) and irinotecanhydrochloride (Daiichi Seiyaku) (100 mg/kg, every four days for threetimes, intravenous) were administered alone or in combination. The majorand minor axes of tumors were measured with Digimatic caliper (MitsutoyoCorporation), and tumor volumes and relative tumor volumes werecalculated according to the following formulae:Tumor Volume (TV)=Major axis of tumor (mm)×(Minor axis of tumor)²(mm²)/2Relative Tumor Volume (RTV)=Tumor volume on measurement day/Tumor volumeon the first administration day.

If statistically significant interaction was observed in the combinationuse group by two-way ANOVA, a synergistic effect was considered toexist.

As a result,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) showed an additive effect when used in combination withirinotecan hydrochloride, and their combination use showed a superioranti-tumor effect as compared with those obtained with4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideor irinotecan hydrochloride alone (Tables 1, 2 and 3, and FIGS. 1, 2 and3). In addition, combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand irinotecan hydrochloride also showed a remarkable anti-tumor effectthat cannot be seen with irinotecan hydrochloride alone (Tables 1, 2 and3, and FIGS. 1, 2 and 3).

TABLE 1 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.36 ± 2.97Compound A 3 mg/kg 4.29 ± 1.51 Irinotecan hydrochloride 1.65 ± 0.51 100mg/kg Compound A 3 mg/kg + 0.97 ± 0.25 p = 0.320 Irinotecanhydrochloride Additive effect 100 mg/kg

TABLE 2 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.36 ± 2.97Compound A 10 mg/kg 2.93 ± 1.55 Irinotecan hydrochloride 1.65 ± 0.51 100mg/kg Compound A 10 mg/kg + 0.72 ± 0.11 p = 0.170 Irinotecanhydrochloride Additive effect 100 mg/kg

TABLE 3 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.36 ± 2.97Compound A 30 mg/kg 1.76 ± 0.92 Irinotecan hydrochloride 1.65 ± 0.51 100mg/kg Compound A 30 mg/kg + 0.51 ± 0.11 p = 0.0760 Irinotecanhydrochloride Additive effect 100 mg/kg

Tables 1, 2 and 3 show anti-tumor effects obtained by the administrationof4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A in Tables 1, 2 and 3) alone, the administration ofirinotecan hydrochloride alone and the combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand irinotecan hydrochloride in HSC-39 subcutaneous transplanted(xenograft) models. The first day of administration was considered Day1.

According to the obtained results, the combination of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand irinotecan hydrochloride can provide a pharmaceutical compositionand a kit that show a remarkable anti-tumor activity, which may be usedfor treating cancer.

EXAMPLE 2 Combination Use of the Compound of the Invention and5-Fluorouracil in Subcutaneous Transplanted (Xenograft) Models (In Vivo)of Human Scirrhous Gastric Cancer Cell Line (HSC-39)

Human scirrhous gastric cancer cell line HSC-39 (purchased fromImmuno-Biological Laboratories Co., Ltd.) was cultured in RPMI1640(containing 10% FBS) in a 5% carbon dioxide gas incubator at 37° C. toabout 80% confluence, and then the cells were collected withtrypsin-EDTA. A 5×10⁷ cells/mL suspension was prepared with a phosphatebuffer, and each 0.1 mL of the resulting cell suspension wassubcutaneously transplanted to nude mice at the side of their bodies.

Thirteen days after the transplantation,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(3, 10 or 30 mg/kg, once a day for four weeks, oral) and 5-fluorouracil(Kyowa Hakko) (50 mg/kg, every four days for three times, intravenous)were administered alone or in combination. The major and minor axes oftumors were measured with Digimatic caliper (Mitsutoyo Corporation), andtumor volumes and relative tumor volumes were calculated according tothe following formulae:Tumor Volume (TV)=Major axis of tumor (mm)×(Minor axis of tumor)²(mm²)/2Relative Tumor Volume (RTV)=Tumor volume on measurement day/Tumor volumeon the first administration day.

If statistically significant interaction was observed in the combinationuse group by two-way ANOVA, a synergistic effect was considered toexist.

As a result,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) showed an additive effect when used in combination with5-fluorouracil, and their combination use showed a superior anti-tumoreffect as compared with those obtained with4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideor 5-fluorouracil alone (Tables 4, 5 and 6, and FIGS. 4, 5 and 6). Inaddition, combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand 5-fluorouracil also showed a remarkable anti-tumor effect thatcannot be seen with 5-fluorouracil alone (Tables 4, 5 and 6, and FIGS.4, 5 and 6).

TABLE 4 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.90 ± 3.12Compound A 3 mg/kg 4.16 ± 1.28 5-Fluorouracil 50 mg/kg 5.16 ± 1.37Compound A 3 mg/kg + 3.02 ± 0.55 p = 0.150 5-Fluorouracil 50 mg/kgAdditive effect

TABLE 5 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.90 ± 3.12Compound A 10 mg/kg 3.73 ± 1.21 5-Fluorouracil 50 mg/kg 5.16 ± 1.37Compound A 10 mg/kg + 2.44 ± 0.70 p = 0.413 5-Fluorouracil 50 mg/kgAdditive effect

TABLE 6 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 9.90 ± 3.12Compound A 30 mg/kg 2.72 ± 1.33 5-Fluorouracil 50 mg/kg 5.16 ± 1.37Compound A 30 mg/kg + 1.43 ± 0.44 p = 0.887 5-Fluorouracil 50 mg/kgAdditive effect

Tables 4, 5 and 6 show anti-tumor effects obtained by the administrationof4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A in Tables 4, 5 and 6) alone, the administration of5-fluorouracil alone and the combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand 5-fluorouracil in HSC-39 subcutaneous transplanted (xenograft)models. The first day of administration was considered Day 1.

According to the obtained results, the combination of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand 5-fluorouracil can provide a pharmaceutical composition and a kitthat show a remarkable anti-tumor activity, which may be used fortreating cancer.

EXAMPLE 3 Combination Use of the Compound of the Invention andPaclitaxel in Subcutaneous Transplanted (Xenograft) Models (In Vivo) ofHuman Scirrhous Gastric Cancer Cell Line (HSC-39)

Human scirrhous gastric cancer cell line HSC-39 (purchased fromImmuno-Biological Laboratories Co., Ltd.) was cultured in RPMI1640(containing 10% FBS) in a 5% carbon dioxide gas incubator at 37° C. toabout 80% confluence, and then the cells were collected withtrypsin-EDTA. A 5×10⁷ cells/mL suspension was prepared with a phosphatebuffer, and each 0.1 mL of the resulting cell suspension wassubcutaneously transplanted to nude mice at the side of their bodies.

Eleven days after the transplantation,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(3, 10 or 30 mg/kg, once a day for four weeks, oral) and paclitaxel(Calbiochem) (14 mg/kg, once a day for five days, intravenous) wereadministered alone or in combination. The major and minor axes of tumorswere measured with Digimatic caliper (Mitsutoyo Corporation), and tumorvolumes and relative tumor volumes were calculated according to thefollowing formulae:Tumor Volume (TV)=Major axis of tumor (mm)×(Minor axis of tumor)²(mm²)/2Relative Tumor Volume (RTV)=Tumor volume on measurement day/Tumor volumeon the first administration day.

If statistically significant interaction was observed in the combinationuse group by two-way ANOVA, a synergistic effect was considered toexist.

As a result,4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A) showed an additive effect when used in combination withpaclitaxel, and their combination use showed a superior anti-tumoreffect as compared with those obtained with4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideor paclitaxel alone (Tables 7, 8 and 9, and FIGS. 7, 8 and 9). Inaddition, combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand paclitaxel also showed a remarkable anti-tumor effect that cannot beseen with paclitaxel alone (Tables 7, 8 and 9, and FIGS. 7, 8 and 9).

TABLE 7 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 10.75 ± 4.94 Compound A 3 mg/kg 3.79 ± 1.43 Paclitaxel 14 mg/kg 4.26 ± 2.06 CompoundA 3 mg/kg + 1.54 ± 0.72 p = 0.929 Paclitaxel 14 mg/kg Additive effect

TABLE 8 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 10.75 ± 4.94 Compound A 10 mg/kg 3.27 ± 1.26 Paclitaxel 14 mg/kg 4.26 ± 2.06 CompoundA 10 mg/kg + 1.21 ± 0.42 p = 0.918 Paclitaxel 14 mg/kg Additive effect

TABLE 9 Relative tumor volume Administered on Day 29 Two-way compoundAverage ± standard deviation ANOVA Control (untreated) 10.75 ± 4.94 Compound A 30 mg/kg 1.69 ± 0.72 Paclitaxel 14 mg/kg 4.26 ± 2.06 CompoundA 30 mg/kg + 0.52 ± 0.13 p = 0.555 Paclitaxel 14 mg/kg Additive effect

Tables 7, 8 and 9 show anti-tumor effects obtained by the administrationof4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide(Compound A in Tables 7, 8 and 9) alone, the administration ofpaclitaxel alone and the combination use of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand paclitaxel in HSC-39 subcutaneous transplanted (xenograft) models.The first day of administration was considered Day 1.

According to the obtained results, the combination of4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamideand paclitaxel can provide a pharmaceutical composition and a kit thatshow a remarkable anti-tumor activity, which may be used for treatingcancer.

According to the results from these examples, a FGFR2 inhibitor,preferably4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,was found to show an excellent anti-tumor activity when used incombination with a therapeutic substance for gastric cancer, preferablyirinotecan, 5-fluorouracil or paclitaxel.

INDUSTRIAL APPLICABILITY

According to the present invention, there is provided a therapeuticagent, a kit and a therapeutic method for undifferentiated gastriccancer that show an excellent anti-tumor activity, use of a FGFR2inhibitor for producing said therapeutic agent, and a FGFR2 inhibitorfor said therapeutic agent.

More particularly, there is provided a therapeutic agent, a kit and atherapeutic method for undifferentiated gastric cancer that show anexcellent anti-tumor activity and that can be used for treatingundifferentiated gastric cancer by combining:

(i) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a therapeutic drug for gastric cancer;

(ii) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a FGFR2 inhibitor that is not comprised in the compoundsrepresented by General Formula (I); or

(iii) a FGFR2 inhibitor such as a FGFR2 inhibitor that is not comprisedin the compounds represented by General Formula (I) and a therapeuticdrug for gastric cancer.

The present invention also provides a pharmaceutical composition and akit for administration to a living organism comprising at least oneselected from the group consisting of a cell overexpressing FGFR2 and acell expressing mutant FGFR2, a method for treating a disease of saidliving organism, use of a FGFR2 inhibitor for producing saidpharmaceutical composition and a FGFR2 inhibitor for said pharmaceuticalcomposition.

More specifically, there is provided a pharmaceutical composition, a kitand a therapeutic method for said living organism that show an excellentanti-tumor activity and that can be used for treating a disease bycombining:

(i) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a therapeutic drug for gastric cancer;

(ii) a FGFR2 inhibitor such as a compound represented by General Formula(I) and a FGFR2 inhibitor that is not comprised in the compoundsrepresented by General Formula (I); or

(iii) a FGFR2 inhibitor such as a FGFR2 inhibitor that is not comprisedin the compounds represented by General Formula (I) and a therapeuticdrug for gastric cancer.

CROSS-REFERENCE TO PRIOR APPLICATION

This is a U.S. National Phase Application under 35 U.S.C §371 ofInternational Patent Application No. PCT/JP2008/051697 filed Jan. 28,2008, which claims the benefit of U.S. Provisional Application No.60/887,006 filed Jan. 29, 2007, both of which are incorporated byreference herein. The International Application was published inJapanese on Aug. 7, 2008 as WO 2008/093855 A1 under PCT Article 21(2).

The invention claimed is:
 1. A method for treating undifferentiatedgastric cancer, characterized by administering effective dosages of4(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,or a pharmacologically acceptable salt thereof, and a therapeuticsubstance selected from the group consisting of irinotecan, paclitaxel,and pharmacologically acceptable salts thereof to a living organism.